Publications by authors named "Mariusz Koda"

88 Publications

Impact of Coronavirus Disease 2019 on Out-of-Hospital Cardiac Arrest Survival Rate: A Systematic Review with Meta-Analysis.

J Clin Med 2021 Mar 15;10(6). Epub 2021 Mar 15.

Department of Research Outcomes, Polish Society of Disaster Medicine, 05-090 Raszyn, Poland.

Out-of-hospital cardiac arrest (OHCA) is a challenge for medical staff, especially in the COVID-19 period. The COVID-19 disease caused by the SARS-CoV-2 coronavirus is highly infectious, thus requiring additional measures during cardiopulmonary resuscitation (CPR). Since CPR is a highly aerosol-generating procedure, it carries a substantial risk of viral transmission. We hypothesized that patients with diagnosed or suspected COVID-19 might have worse outcomes following OHCA outcomes compared to non-COVID-19 patients. To raise awareness of this potential problem, we performed a systematic review and meta-analysis of studies that reported OHCA in the pandemic period, comparing COVID-19 suspected or diagnosed patients vs. COVID-19 not suspected or diagnosed group. The primary outcome was survival to hospital discharge (SHD). Secondary outcomes were the return of spontaneous circulation (ROSC), survival to hospital admission or survival with favorable neurological outcomes. Data including 4210 patients included in five studies were analyzed. SHD in COVID-19 and non-COVID-19 patients were 0.5% and 2.6%, respectively (odds ratio, OR = 0.25; 95% confidence interval, CI: 0.12, 0.53; < 0.001). Bystander CPR rate was comparable in the COVID-19 vs. not COVID-19 group (OR = 0.88; 95% CI: 0.63, 1.22; = 0.43). Shockable rhythms were observed in 5.7% in COVID-19 patients compared with 37.4% in the non-COVID-19 group (OR = 0.19; 95% CI: 0.04, 0.96; = 0.04; I = 95%). ROSC in the COVID-19 and non-COVID-19 patients were 13.3% vs. 26.5%, respectively (OR = 0.67; 95% CI: 0.55, 0.81; < 0.001). SHD with favorable neurological outcome was observed in 0% in COVID-19 vs. 3.1% in non-COVID-19 patients (OR = 1.35; 95% CI: 0.07, 26.19; = 0.84). Our meta-analysis suggests that suspected or diagnosed COVID-19 reduces the SHD rate after OHCA, which seems to be due to the lower rate of shockable rhythms in COVID-19 patients, but not due to reluctance to bystander CPR. Future trials are needed to confirm these preliminary results and determine the optimal procedures to increase survival after OHCA in COVID-19 patients.
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http://dx.doi.org/10.3390/jcm10061209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001432PMC
March 2021

Tumor-infiltrating lymphocytes in tissue material combined with systemic lymphocyte inflammation in patients with colorectal cancer.

Mol Clin Oncol 2021 May 12;14(5):97. Epub 2021 Mar 12.

Department of Medical Pathomorphology, Medical University of Bialystok, 15-269 Bialystok, Poland.

The efficacy of cancer immunotherapy has been actively explored in the treatment of various malignant neoplasms of the gastrointestinal tract. In light of recent reports, the present study aimed to investigate the combination of the absolute lymphocyte count (ALC), percentage of tumor-infiltrating lymphocyte (TILs) and tumor progression status in patients with colorectal cancer (CRC) who underwent surgery. The medical records of 160 patients diagnosed with CRC were retrospectively reviewed. TILs were determined as a percentage of mononuclear inflammatory cells in the total intratumoral or stromal area as determined in five high power fields (magnification, x200-400), at the invasive front and in the centre of the tumour. Blood samples were obtained within 3 days prior to and 7 days following the surgical treatment. The assessment of the TIL percentage was performed in the tissue at the invasive front and in the centre of the primary tumour mass in combination with the determination of ALC in whole blood samples. The samples were obtained prior to and after surgery from patients with CRC, and the tumour progression status was also assessed (TILs/ALC/tumour progression status). A significant association was observed between the percentage of TILs in the main mass of tumour and the tumour size (P=0.031), the pT stage (P=0.049) and the incidence of necrosis (P=0.037) following surgery. The histological type was associated with the evaluated combined parameters prior to surgery (P=0.046). Lymph node pouch invasion was associated with TILs at the invasive front of tumour and with ALC prior to and after surgery (P=0.006 and P=0.037). Furthermore, the data indicated that the percentage of TILs located on the invasive front and centre of the tumour, and the ALC prior to and following surgery correlated with the treatment status (P=0.032, P=0.018, P≤0.001 and P≤0.001). A significant association was noted between eight features and evaluated combined parameters following surgery. These included the tumour size (P=0.021), TNM stage (P<0.001), tumour deposits (P=0.001), incidence of necrosis (P=0.042) and lymph node metastasis (P<0.001). Furthermore, the degree of invasion of venous (P<0.001), lymphatic (P<0.001) and perineural (P<0.001) sites was also significantly associated with TILs, ALC obtained after surgical treatment and tumor progression status. The data demonstrated that local and systemic chronic inflammation was associated with tumour progression in patients with CRC.
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http://dx.doi.org/10.3892/mco.2021.2259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976436PMC
May 2021

Review on significance of GDNF, PTCH1 and RNF213 in chromophobe renal cell carcinoma illustrated by the case of 71-years-old man.

Pol J Pathol 2020 ;71(3):195-199

Department of General Pathomorphology, Collegium Pathologicum, Medical University of Bialystok, Bialystok, Poland.

Here we review the role of GDNF, PTCH1, RNF213 illustrated by a case of renal cell carcinoma, chromophobe type (pT2a 8th pTNM edition) of the left kidney of 71-year-old man. Status of potential hotspots in 409 tumor genes were studied by means of next generation sequencing (NGS) technology (IonTorrent - Thermo Fisher Scientific, USA) using Ion AmpliSeq™ Comprehensive Cancer Panel. Next-generation sequencing (NGS) revealed mutations of GDNF (NM_001190468: c. 328C>T, p.R110W, allelic frequency 46%), PTCH1 (NM_001083607:c. 2969C
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http://dx.doi.org/10.5114/pjp.2020.99785DOI Listing
January 2021

The intensification of anticancer activity of LFM-A13 by erythropoietin as a possible option for inhibition of breast cancer.

J Enzyme Inhib Med Chem 2020 Dec;35(1):1697-1711

Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland.

Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton's tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.
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http://dx.doi.org/10.1080/14756366.2020.1818738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717683PMC
December 2020

Pre- and postoperative neutrophil and lymphocyte count and neutrophil-to-lymphocyte ratio in patients with colorectal cancer.

Mol Clin Oncol 2020 Nov 25;13(5):56. Epub 2020 Aug 25.

Department of Pathomorphology, Comprehensive Cancer Center, Medical University of Bialystok, 15-027 Bialystok, Poland.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR) in pre- and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease- free survival (DFS). The variables pre- and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P<0.001). PreNEU count correlated with tumor size, necrosis and tumor budding (R=0.204, P=0.014; R=0.189, P=0.023; R=-0.174, P=0.036, respectively). Moreover, postNEU was associated only with the histological type (R=0.174; P=0.047). The PreLYMPH count was correlated with distant metastasis (R=-0.153, P=0.046). PreNLR and postNLR were associated with the expression of various histological markers of disease progression. Analysis of DFS indicated that the postNEU count in the low group exhibited a tendency to lower DFS duration, although the results were not significant (P=0.055). In conclusion, the present study indicated a significant correlation between the factors analyzed in blood samples of CRC patients and the disease progression markers.
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http://dx.doi.org/10.3892/mco.2020.2126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468214PMC
November 2020

Monocyte-to-lymphocyte ratio as a prognostic factor in peripheral whole blood samples of colorectal cancer patients.

World J Gastroenterol 2020 Aug;26(31):4639-4655

Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok 15027, Poland.

Background: Colorectal cancer is the third most common malignancy worldwide. Therefore, it is critically important to identify new useful markers that can be easily obtained in routine practice. Inflammation is a crucial issue in the pathogenesis and development of cancer.

Aim: To evaluate the prognostic value of absolute monocyte count, monocyte to lymphocyte ratio (MLR), the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (NLR-PLR), and combined platelet and neutrophil-to-lymphocyte ratio (PLT-NLR) in peripheral blood samples of patients with colorectal cancer undergoing surgery.

Methods: We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery, and 42 healthy controls. The status of absolute monocyte count, MLR, NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery. Haematologic factors were examined in correlation with the type of tumour growth, tumour size, histological type, percentage of mucinous component, grade of malignancy, Tumour-Node-Metastasis stage, venous, lymphatic and perineural invasion of cancer cells, status of lymph node invasion and the presence of cancer cell deposits. The Kaplan-Meier method and the long-rank test were used to compare survival curves. To determine independent prognostic factors, univariate and multivariate Cox proportional hazards regression models were applied.

Results: The PLT-NLR status was correlated with tumour size and the presence of perineural invasion ( = 0.015; = -0.174, = 0.037). Moreover, high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component (NLR-PLR: = 0.002; = 0.009; PLR-NLR status: = 0.002; = 0.007). The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery [HR = 2.903, 95%CI: (1.368-6.158), = 0.005] and the status of lymph node metastasis [HR = 0.813, 95%CI: (0.653-1.013), = 0.050] were independent prognostic factors in colorectal cancer patients.

Conclusion: The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.
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http://dx.doi.org/10.3748/wjg.v26.i31.4639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445871PMC
August 2020

Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression.

World J Gastroenterol 2020 Jul;26(28):4140-4150

Department of General Pathomorphology, Medical University of Bialystok, Bialystok 15269, Poland.

Background: Despite effective prevention and screening methods, the incidence and mortality rates associated with colorectal cancer (CRC) are still high. Insulin receptor substrate 1 (IRS-1), a signaling molecule involved in cell proliferation, survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models. However, the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined.

Aim: To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers, Bax, Bcl-xL and Ki-67 are related to clinicopathological features in human CRC.

Methods: The expression of IRS-1, Bax, Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods. The assays were performed using specific antibodies against IRS-1, Bax, Bcl-xL, Ki-67. The associations between the expression of IRS-1, Bax, Bcl-xL, Ki-67 were analyzed in relation to clinicopathological parameters, , patient age, sex, primary localization of tumor, histopathological type, grading, staging and lymph node spread. Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at < 0.05.

Results: Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases. IRS-1 expression at any level in primary CRC was associated with tumor grade (69% in moderately differentiated tumors, G2 31% in poorly differentiated tumors, G3) and with histological type (81.9% in adenocarcinoma 18.1% in adenocarcinoma with mucosal component cases). Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases (95.1%) and in moderately differentiated tumors (85.2%). We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined. The relationships between studied proteins were related to clinicopathological parameters of CRC. No significant correlation between the expression of IRS-1 and proliferation marker Ki-67, excluding early stage tumors, where the correlation was positive and on a high level ( = 0.043, = 0.723).

Conclusion: This study suggests that IRS-1 is co-expressed with both pro- and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC.
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http://dx.doi.org/10.3748/wjg.v26.i28.4140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403795PMC
July 2020

Analysis of mutations of PARP1, RNF213, PAX8, KMT2C, MTRR in malignant mesothelioma of testicular tunica vaginalis testis.

Pol J Pathol 2020 ;71(1):69-74

Department of Clinical Oncology, Holy Cross Oncology Centre, Kielce, Poland.

Molecular next gene sequencing was used to evaluate mutations in 409 common mutated cancer-related genes in malignant mesothelioma of tunica vaginalis testis (MMTVT) of 81-year-old man. Multifocal papillary-solid areas contained necrosis among highly cellular fields with multiple mitoses. It was positive for WT1, CKAE1/AE3, calretinin, CK7 with negativity for CK5, PSA, TTF-1. Following mutations were revealed in PARP1 (NM_001618: c.2285TG, p.K135R), MTRR (NM_024010: c.147A>G, p.I49M) and two sorts of mutations in structure of KMT2C gene (NM_170606: c.2447_2448insA (c.2447dupA), p.Y816fs and NM_170606: c.1042G>A, p.D348N) for the first time in MMTVT.
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http://dx.doi.org/10.5114/pjp.2020.95418DOI Listing
September 2020

Review of Potential Significance of Mutations of , and Detected Using Next Generation Sequencing (NGS) in Dermal Fibrosarcoma Arising in Dermatofibrosarcoma Protuberans.

Folia Med (Plovdiv) 2020 Mar;62(1):17-22

Holy Cross Oncology Centre, Kielce, Poland.

We examined a status of fibrosarcoma arising in dermatofibrosarcoma protuberans of 64-year-old male patient. A dermal, solid, grayish-yellow, desmin-negative trichrome-bluish tumor measured 1.5 cm in diameter pT1a (edition 8 pTNM). It was composed of spindle cells. It was consistent with dermatofibrosarcoma protuberans (ICD-O3: 8832/3) in areas of low mitotic activity, low atypia and sustained CD34 positivity. CD34-negative texture with high mitotic index and atypia was consistent with the high grade sarcoma apparently of fibrous origin, given category of poorly differentiated fibrosarcoma. The high grade component was graded (G3) and scored according to French Federation of Cancer Centers Sarcoma Group (FNCLCC): total score of 6 points: tumor differentiation: 3 points + Mitotic count: 3 points (up to 26 mitoses/ 10HPF in high-grade fields), + no necrosis: 0 points. In low grade sarcomatous component ADAMTS20 (NM_025003: c.1661C>T, p.P554L) NF1 (NM_001042492: c. 2173G>T, p.E725X) and PKHD1 (NM_138694: c. 11074C>T, p.R3692X) were revealed with following allelic frequencies: 25%, 27% and 17%. In high grade component allelic frequencies of the same mentioned mutations were 30%, 30% and 14% respectively. In the light of our findings, none of detected mutations can be regarded as a mutation that would definitely induce phenotype of high malignancy, because ADAMTS20, NF1 and PKHD1 mutations were detected both in high grade sarcoma and in low grade areas of dermatofibrosarcoma protuberans. It also points that these mutations appeared on early stages of tumor development.
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http://dx.doi.org/10.3897/folmed.62.e48003DOI Listing
March 2020

Tumor-infiltrating lymphocytes in primary tumors of colorectal cancer and their metastases.

Exp Ther Med 2019 Dec 30;18(6):4904-4912. Epub 2019 Oct 30.

Department of Pathomorphology, Comprehensive Cancer Center, 15-027 Bialystok, Poland.

The presence of tumor cells in the large intestine stimulates hypoxia and local inflammatory mediators that activate numerous inflammatory cells, including a diverse lymphoid tumor cell population. The aim of the present study was to evaluate tumor-infiltrating lymphocytes (TILs) located in the invasive primary tumor, surrounding deposits of tumor cells and those present in distal metastatic cells in the liver of patients with colorectal cancer. Furthermore, the correlation of TILs with anatomical parameters was assessed. The study group included 123 patients with primary tumor colorectal cancer without distant metastasis, 25 cases with deposits of colorectal cancer cells and 15 cases of colorectal cancer liver metastasis. TILs were assessed in tissues stained with hematoxylin-eosin using light microscopy and evaluated by two independent pathologists blinded to the clinical information. Infiltration of TILs in the invasive front of primary tumor was stronger compared with those surrounding deposits of cancer cells and liver metastases (P<0.001). TILs in the invasive front of primary tumor masses were associated with various variables linked with tumor progression and inflammatory cell infiltrate. TILs distributed around the deposits of cancer cells were associated with postoperative treatment; however, those localized in the invasive front of liver metastases were correlated with preoperative therapy. In conclusion, TILs assessment in primary tumors of colorectal cancer, surrounding deposits of tumor cells and in the metastatic cells in the liver may be helpful in understanding the role of these cells in the organization of immune response.
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http://dx.doi.org/10.3892/etm.2019.8146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878893PMC
December 2019

Prognostic significance of inflammatory cell response in patients with colorectal cancer.

Oncol Lett 2019 Jul 13;18(1):783-791. Epub 2019 May 13.

Department of Pathomorphology, Comprehensive Cancer Center, 15-027 Białystok;, Poland.

Cancer cells are characterized by a low antigenic immunogenicity, a rapid growth and an immunosuppressive effect on the extracellular matrix. These properties induce a weak immune response in colorectal cancer (CRC) carcinogenesis. It is therefore crucial to determine the composition of the inflammatory mass, including neutrophils, macrophages and eosinophils in the tumor tissue of patients with CRC, and to analyze other clinicopathological parameters. The present study included 144 patients diagnosed with CRC. Tissue samples obtained from routine histopathological diagnosis were stained with hematoxylin and eosin. Inflammatory cells were assessed in the invasive front and in the center of the tumor by light microscopy under a high-power magnification. The percentage of neutrophils in the invasive front was significantly higher compared with that in the center of the tumor mass (P<0.01). Macrophages and eosinophils were present in the invasive front and in the center of tumor mass in most cases. The presence of neutrophils, macrophages and eosinophils was correlated with various clinicopathological features. Patients with macrophages present in the center of tumor mass had longer disease-free survival time (P=0.041). In conclusion, the present study demonstrated that the inflammatory cell infiltrate served a significant role in the immune response of patients with CRC. It should be noted that the presence of macrophages localized in the stroma of the central part of the primary tumor mass was associated with the survival time of patients with CRC.
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http://dx.doi.org/10.3892/ol.2019.10343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540326PMC
July 2019

Features of the fetal gonad in androgen synthesis in the postpubertal testis are preserved in complete androgen insensitivity syndrome due to a novel genetic splice site donor variant in androgen receptor gene intron 1.

J Steroid Biochem Mol Biol 2019 10 5;193:105420. Epub 2019 Jul 5.

Department of Reproduction and Gynaecological Endocrinology, Medical University of Bialystok, Poland.

Mutations in the X-linked androgen receptor (AR) gene cause complete androgen insensitivity syndrome (CAIS). CAIS may cause congenital sexual development disorder, which frequently develops into testicular tumors. Here, we describe a novel splice-site intron 1 mutation in AR leading to improper splicing and AR protein absence in CAIS gonads. We characterized a patient's postpubertal gonadal steroidogenic enzyme expression profile. Localization of both CYP11A1 and CYP17A1 enzymes was restricted to both Leydig tumor cells and adjacent to tumor gonadal tissues. Sertoli cells of the CAIS gonad showed abundant HSD17B3 protein, which is an adult Leydig cell marker that enables the conversion of androstenedione to testosterone. Such HSD17B3 expression is typical for fetal-type Sertoli cells in rodents. The postpubertal CAIS gonad of our patient was completely devoid of androgen signaling pathway activity. Plausibly, the postpubertal Leydig cells consisted of two distinct cell populations: postpubertal fetal-type Leydig cells that persisted as androgen-independent cells and immature adult Leydig cells that failed to differentiate. Taken together, in this CAIS postpubertal testis, both Leydig and fetal-type Sertoli cells participated in testosterone production. Our results indicate the importance of molecular analysis as well as the characterization of steroidogenic enzyme profiling in the CAIS patient's gonad.
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http://dx.doi.org/10.1016/j.jsbmb.2019.105420DOI Listing
October 2019

Review on Retinal Gliosis Illustrated with a Series of Massive Glioses and Focal Nodular Gliosis Cases in Regard to Potential Pitfalls of Ocular Reactive Tumor-like Lesions of this Type.

Folia Med (Plovdiv) 2018 Mar;60(1):30-38

Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland.

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.
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http://dx.doi.org/10.1515/folmed-2017-0061DOI Listing
March 2018

Squamous cell carcinoma of the breast as a clinical diagnostic challenge.

Mol Clin Oncol 2018 Apr 22;8(4):587-591. Epub 2018 Feb 22.

Department of Pathomorphology, Comprehensive Cancer Center, 15-027 Białystok, Poland.

Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice.
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http://dx.doi.org/10.3892/mco.2018.1581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844120PMC
April 2018

Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma.

Oncol Lett 2017 Dec 21;14(6):6421-6432. Epub 2017 Sep 21.

Department of Pathomorphology, Comprehensive Cancer Center, 15-027 Bialystok, Poland.

The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations.
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http://dx.doi.org/10.3892/ol.2017.7013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680638PMC
December 2017

Comparison of E-cadherin with STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different ER-alpha immunoprofile.

Gynecol Endocrinol 2018 Feb 22;34(2):171-174. Epub 2017 Sep 22.

a Department of General Pathomorphology , Medical University of Bialystok , Bialystok , Poland.

E-cadherin is a factor of good prognosis in endometrioid adenocarcinomas, while STAT3 is an oncogenic driver of carcinogenesis. E-cadherin, Bak, Bcl-xL and STAT3 were immunohistochemically detected in 78 human endometrioid adenocarcinomas. E-cadherin correlated with STAT3 (p <. 001, r = 0.537) as well as Bak (p = .005, r = 0.314) and Bcl-xL (p = .002, r = 0.340) in the whole study group. In G2 tumors, E-cadherin associated with Bak (p = .021, r = 0.319), Bcl-xL (p = .026, r = 0.309) and STAT3 (p <.001, r = 0.513) but not in G3 adenocarcinomas. E-cadherin correlated with Bak and Bcl-xL in both G1- and estrogen receptor (ER)-negative tumors with significant relation of E-cadherin and STAT3 in G1- and ER-negative tumors. Antigrowth synergy of expression was preserved for antiapoptotic Bak and proliferation-suppressing E-cadherin in IA adenocarcinomas (p = .031, r = 0.342) with no significance between Bak and E-cadherin or STAT3 and emerging correlation between E-cadherin and Bcl-xL in IB + II tumors instead (p = .003, r = 0.472). E-cadherin correlated with Bak and Bcl-xL in ER-positive adenocarcinomas (p =  .002, r = 0.382 and p <.001, r = 0.439, respectively) but not in ER-negative tumors. In conclusion, expression deregulation of studied proteins is reflected in selective loss of correlation between suppressors of tumor growth (E-cadherin and Bak) presumably due to progressing impairment of growth-inhibitory properties of clone of neoplastic cells within higher staging and poorer differentiation.
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http://dx.doi.org/10.1080/09513590.2017.1379494DOI Listing
February 2018

Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer.

Oncol Lett 2017 Sep 20;14(3):3869-3877. Epub 2017 Jul 20.

Department of Pathomorphology, Comprehensive Cancer Center, Bialystok, Poland.

The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC). In addition, the correlation between cellular inflammatory infiltration, and anatomoclinical and histopathological features of patients was evaluated. The study involved 160 patients diagnosed with primary operable CRC. The local inflammatory infiltrate was assessed in the invasive front and center of the tumor using light microscopy with hematoxylin and eosin (H&E) staining, according to the Klintrup-Makinen criteria, tumor stroma percentage, and Glasgow microenvironment score. The inflammatory infiltrate in the invasive front of the tumor was correlated with gender (P=0.018), the invasion of blood vessels (P=0.020) and lymph vessels (P=0.038), the presence of tumor-infiltrating lymphocytes in the invasive front (P=0.033) and center (P<0.001) of the tumor, fibrosis (P<0.001), and the degree of desmoplasmic stroma (P=0.004). In contrast, inflammatory infiltration in the center of the tumor was associated with the tumor node metastasis stage (P=0.012), Dukes' stage (P=0.009), primary tumor stage (P=0.036), lymph node status (P=0.005), number of lymph nodes (P=0.006), invasion of lymph node pouches (P=0.021), size of lymph node metastasis (P=0.025) and the degree of desmoplasmic stroma (P=0.002). The low-group, who demonstrated an absent or weak inflammatory cell infiltrate in the invasive front of the tumor, had a statistically significant shorter disease-free survival (DFS) time (P=0.004). Inflammatory cell infiltrate in the invasive front was identified as an independent predictive factor in CRC (P=0.041). In conclusion, the degree of inflammatory cell infiltration in the invasive front of the primary tumor significantly affects various variables that determine disease progression and DFS rates of patients with CRC. Furthermore, the routine histopathological assessment of this parameter in tissue stained with H&E may have potential prognostic value.
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http://dx.doi.org/10.3892/ol.2017.6639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588066PMC
September 2017

Role of periostin in esophageal, gastric and colon cancer.

Oncol Lett 2016 Aug 9;12(2):783-787. Epub 2016 Jun 9.

Department of General Pathomorphology, Medical University of Białystok, Białystok, Podlaskie 15-269, Poland.

Periostin, also known as osteoblast-specific factor 2, is a cell-adhesion protein with pleiotropic properties. The protein serves a vital role in the maintenance and development of tooth and bone tissue, in addition to cardiac development and healing. Periostin levels are increased in several forms of cancer, including pancreatic, ovarian, colon, lung, breast, gastric, thyroid, and esophageal head and neck carcinomas. The present review highlights the key role of periostin in tumorigenesis, particularly in increasing cell survival, invasion, angiogenesis, epithelial-mesenchymal transition and metastasis of carcinoma cells by interacting with numerous cell-surface receptors, including integrins, in the phosphoinositide 3-kinase-Akt pathway. In addition, periostin actively affects the canonical Wnt signaling pathway of colorectal tumorigenesis. The current review focused on the involvement of periostin in the development of colorectal, esophageal and gastric cancer.
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http://dx.doi.org/10.3892/ol.2016.4692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950105PMC
August 2016

Eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 can depend on ER-alpha overexpression in human endometrioid adenocarcinoma.

Gynecol Endocrinol 2015 21;31(8):604-8. Epub 2015 Aug 21.

a Department of General Pathomorphology , Medical University of Bialystok , Bialystok , Poland .

Estrogen receptor (ER) and progesterone receptor (PgR) accumulations lead to impairment of gap junctional intercellular communication in endometrial cancer. The task of this study was to explore relationships of Cx26 and Cx43 with anti-apoptotic protein Bcl-xL and proapoptotic agent Bak in ER-alpha and PgR negative or variably positive endometrioid adenocarcinomas. Cx26, Cx43, Bak, Bcl-xL, PgR and ER-alpha were detected in 78 endometrioid adenocarcinomas with immunohistochemistry. There was a remarkable cellular re-distribution of Cx26 and Cx43 from normally membranous location in normal endometrium to aberrantly cytoplasmic expression in endometrioid adenocarcinomas, thus suggesting the decrease of functional membranous gap junctions in the malignancy. Bak failed to correlate with Cx43 regardless of either PgR or ER-alpha status of tumors, while Bcl-xL positively correlated with Cx43 in ER-alpha positive tumors (p = 0.001, r = 0.427) and both PgR positive (p = 0.019, r = 0.312) and negative (p = 0.015, r = 0.509) cancers. Similarly, Bcl-xL significantly associated with Cx26 in ER-alpha positive tumors (p = 0.036, r = 0.267) and both PgR positive (p = 0.026, r = 0.297) and negative (p = 0.046, r = 0.429) cancers. On the contrary, Bak exclusively correlated with Cx26 only in ER-alpha negative tumors (p = 0.027, r = 0.551). ER-alpha status of endometrioid adenocarcinomas could restrict eventual proapoptotic or anti-apoptotic impact of aberrantly expressed Cx43 and Cx26 in these tumors.
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http://dx.doi.org/10.3109/09513590.2015.1017811DOI Listing
July 2016

Adenoid basal carcinoma-like tumor combined with invasive squamous cell carcinoma foci of uterine cervix - a case report of 55-year-old woman with literature review.

Rom J Morphol Embryol 2014 ;55(3 Suppl):1225-30

Department of Anatomy, Faculty of Health Sciences, Jan Kochanowski Memorial University, Kielce, Poland;

Background: Adenoid basal carcinoma (ABC) of uterine cervix is an extraordinary example of carcinoma with both basal and glandular cell types. Here we present such a case of ABC combined with invasive squamous cell carcinoma (SCC) of 55-year-old woman.

Methods: The tumor was stained with Hematoxylin-Eosin (HE), Mucicarmine, PAS/Alcian Blue, CK AE1/AE3, CK7, CD117 and Ki67.

Results: The whitish-grey 1 cm in-depth infiltration of endocervix was composed of infiltrative coalescing areas of CK AE1/AE3 positive carcinoma with peripheral palisading of basal cell type with spaces lined by Mucicarmine- and Alcian Blue-positive benign looking, glandular epithelium. There were also foci of apparently malignant squamous epithelium with evident dyskeratosis. Thus, a lesion was diagnosed of adenoid basal carcinoma combined with invasive squamous cell carcinoma foci of uterine cervix. The tumor was further CD117 negative what favored diagnosis of ABC over adenoid cystic carcinoma (ACC). There were rare mitoses on HE slides but 60% of all tumor cells were positive for Ki67 that would partially contradict reported benign nature of ABC lesion. Moreover, tumor was CK7-positive and this finding was controversial and according to one report favored diagnosis of ABC-like adenosquamous carcinoma (ACC). Due to CK7 positivity and high index of Ki67, the neoplasm was re-classified as adenoid basal carcinoma-like tumor.

Conclusions: It seems reasonable to treat the patient in the same manner as in case of pure simple invasive squamous cell carcinoma because much more aggressive, minor component of invasive SCC was found within ABC in our case.
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September 2015

Immunohistochemical study of KiSS1 and KiSS1R expression in human primary breast cancer: Association with breast cancer receptor status, proliferation markers and clinicopathological features.

Histol Histopathol 2015 Jun 23;30(6):715-23. Epub 2014 Dec 23.

Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Poland.

Recent studies have raised doubts about the protective role of KiSS1/KiSS1R in breast malignancy progression. However, the role of the KiSS1/KiSS1R system in primary breast cancer remains largely unknown. The aim of the present study was to characterize the biology and invasiveness potential of primary breast cancer through evaluation of KiSS1/KiSS1R protein expression and cellular localization with regard to lymph node metastasis status, receptor status (ERs, PR and HER-2/neu), and expression of aromatase, MMP-9, Ki-67 and Cyclin D1 in primary invasive breast cancer tissues. We showed increased protein expression of both KiSS1/KiSS1R and MMP-9 in the cancerous tissues compared with noncancerous tissue adjacent to the breast tumour. In the studied group of breast cancer samples, we observed a positive correlation between KiSS1 and MMP-9. We also showed a positive correlation between KiSS1R and aromatase expression in all studied breast cancers. We did not notice any associations between system and cell cycle regulators. KiSS1/KiSS1R did not correlate either with Cyclin D1 and Ki-67 or with receptor status. However, we showed higher levels of KiSS1R expression in ERα-negative cases than in ERα-positive cases in patients with lymph node metastasis. Present data do not confirm the protective role of KiSS1/KiSS1R in breast cancer progression, but our results do support the hypothesis that the KiSS1/KiSS1R system is activated even in primary breast cancer and sustained during invasion to local lymph nodes.
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http://dx.doi.org/10.14670/HH-30.715DOI Listing
June 2015

E-cadherin and β-catenin adhesion proteins correlate positively with connexins in colorectal cancer.

Oncol Lett 2014 Jun 14;7(6):1863-1870. Epub 2014 Mar 14.

Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland.

The majority of solid cancers present with qualitative and quantitative aberrations of adhesion proteins, including E-cadherin and β-catenin, and connexin (Cx) gap junction proteins, which is consistent with alterations in the expression and location of such proteins in neoplastic cells. Since there are no data on the correlation between adhesion proteins and Cxs in human colorectal cancer (CRC), the aim of the present study was to evaluate the expression and correlation between these proteins. Tissue specimens were obtained from 151 cases of surgically removed colorectal adenocarcinomas. The samples were examined by immunohistochemistry with the use of antibodies against E-cadherin, β-catenin and the three Cxs: Cx26, Cx32 and Cx43. The aberrant expression of the studied adhesion proteins (primarily cytoplasmic for E-cadherin and cytoplasmic and/or nuclear for β-catenin) was observed, whereas only a minority of cases revealed normal membranous distribution of the labeling. The present study is the first in the literature to reveal a correlation between the expression of E-cadherin and β-catenin and the examined Cxs in CRC in humans. The positive correlation between the Cxs, particularly Cx26 and Cx32, and the adhesive proteins occurred in patients without lymph node metastases and in the moderately differentiated tumors (G2). Such a dependency was not observed in the analysis of the correlation between Cx43 and E-cadherin. However, a positive correlation between these proteins was observed in patients with lymph nodes metastases. Additionally, a link between the expression of these adhesion proteins was observed. The present study indicates, for the first time, that the expression of adhesion proteins, E-cadherin and β-catenin, is closely associated with the expression of three studied Cxs in CRC, and that this correlation may improve an understanding of the carcinogenic process in this cancer.
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http://dx.doi.org/10.3892/ol.2014.1970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049722PMC
June 2014

The relationships between hypoxia-dependent markers: HIF-1alpha, EPO and EPOR in colorectal cancer.

Folia Histochem Cytobiol 2013 ;51(4):320-5

Department of General, Medical University of Bialystok, Poland.

Hypoxia triggers production of several cytoprotective proteins. Hypoxia-inducible factor 1alpha (HIF-1α) is a powerful stimulator of transcription of many genes, including erythropoietin (EPO) in hypoxia-affected cells. Recent data have also implicated signaling by EPO receptor (EPOR) as a new factor influencing tumor progression. The aim of the study was to detect by immunohistochemistry the presence of HIF-1α, EPO and EPOR in colorectal cancer (CRC) in reference to clinicopathological variables. We found the presence of the studied proteins in specimens of all 125 CRC patients which is suggestive of the occurrence of hypoxia in colorectal cancer tissues. The expression of HIF-1α correlated significantly with the presence of EPO and EPOR in all samples (P < 0.001, r = 0.549 and P < 0.001, r = 0.536, respectively). Significant correlations (from P < 0.024 to P < 0.001) were found in the analyses of CRC subgroups such as histopathological type tumor, tumor grade, tumor stage and patients with lymph nodes metastases. The same high significant correlations (P < 0.001) were observed in group of sex, age and tumor location. However, the values of the correlation coefficients (r) which usually ranged from 0.5 to 0.6 suggest the existence of independent or concurrent mechanism stimulating generation of these proteins in colorectal cancer.
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http://dx.doi.org/10.5603/FHC.2013.0043DOI Listing
September 2014

Altered expression of ERs, aromatase, and COX2 connected to estrogen action in type 1 endometrial cancer biology.

Tumour Biol 2013 Dec 20;34(6):4007-16. Epub 2013 Jul 20.

Department of Biology and Pathology of Human Reproduction in Bialystok, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Sklodowskiej 24A, 15-276, Bialystok, Poland,

In order to study estrogen-driven microenvironment associated with type 1 endometrial carcinoma, we evaluated estrogen receptors (ERs), aromatase, and cyclooxygenase II (COX2) molecular and immunohistochemical profiles with correlation to clinicopathological features. We investigated aromatase, ERα, ERβ, and COX2 expression at the mRNA and protein levels using quantitative real-time PCR and immunohistochemical method in 51 endometrial carcinomas and 16 normal endometria. All the studied tumors, as well as normal endometria, expressed ERα, ERβ, and COX2 mRNAs. Five endometrial carcinoma tissues and one normal endometrium showed no aromatase mRNA expression. The majority of tumors expressed ERα (82%), aromatase (80%), and COX2 (88%) proteins. Forty-one percent of the studied tumors were ERβ-negative. ERα and ERβ showed significantly decreased mRNA and protein expression levels in endometrial carcinoma as compared to normal endometrium. An opposite trend was shown for COX2 and aromatase proteins. ERα expression correlated positively with COX2 expression at both mRNA and protein levels (P < 0.005, r = 0.398; P < 0.0005, r = 0.510, respectively). There was also a positive correlation between COX2 and aromatase expression in cancer tissue (P < 0.002, r = 0.433 for transcriptional level; P < 0.0005, r = 0.614 for protein level). We observed positive correlations between ERβ and ERα, as well as between ERβ and COX2 at the transcriptional level only (P < 0.0005, r = 0.644; P < 0.002, r = 0.444, respectively). Negative correlations were found between pT category of primary tumor and levels of ERα and ERβ transcripts (P < 0.02, r = -0.332; P < 0.02, r = -0.348, respectively). A negative association between ERβ and the International Federation of Gynecology and Obstetrics (FIGO) staging was also found. The growth of EC1 with the presence of ERα and overexpression of aromatase and COX2 is dependent on estrogens. We believe that ERβ may be considered as a potential marker in the progression of disease in endometrial cancer patients.
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http://dx.doi.org/10.1007/s13277-013-0991-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858613PMC
December 2013

Comparison of primarily diet-modifiable intestinal factors, connexin 43 and E-cadherin with TP53 and TGFB1 in colorectal cancer.

Hepatogastroenterology 2013 Jul-Aug;60(125):1053-7

Background/aims: Primarily, a diet (particularly dietary lipids and vitamins) can reversibly modify intestinal expressions of a few factors like connexin 43 (Cx43), E-cadherin (Cdh1), TP53 and TGFB1 with a special impact on immunity and mutagenesis. Malignant phenotype constitutes a diet-resistant signal streaming with engagement of these molecules which are generated in autonomous ways in colorectal cancer.

Methodology: We aimed to compare adhesion proteins: (Cx43) and Cdh1 with TP53 and TGFB1 in colorectal adenocarcinomas. GJA1P1 and Cdh1 with TP53 and TGFB1 were detected with immunohistochemistry in the study of 106 colorectal adenocarcinomas.

Results: There was aberrant cytoplasmic expression instead of membranous one of Cx43 and Cdh1 reflecting constitutive destruction of intercellular ties while TP53 showed nuclear expression and TGFB1 accumulated in the cytoplasm. TP53 did not correlate with Cx43 (r=0.083, p=0.397) but correlated with Cdh1 (r=0.199, p=0.041). Cdh1 associated with TGFB1 reaching almost statistical significance (r=0.188, p=0.054), while TGFB1 correlated with Cx43 (r=0.359, p=0.001).

Conclusions: The consequent and constant impairment of cancer intercellular communication seems to engage correlated with each other expressions of Cx43 and TGFB1 in colorectal cancer cells.
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http://dx.doi.org/10.5754/hge11162DOI Listing
January 2014

The TIMP-1 expression in germinal centers of hypertrophied adenoids in children.

Int J Pediatr Otorhinolaryngol 2013 Mar 11;77(3):384-8. Epub 2013 Jan 11.

Department of Paediatric Otorhinolaryngology, Medical University of Białystok, Waszyngtona 17, 15-273 Białystok, Poland.

Objectives: The main aim of this study was to evaluate TIMP-1 expression in germinal centers of hypertrophied adenoids in children on the assumption that it can be treated as a marker of adenoidal tissue function.

Patients And Methods: The study involved 54 children undergoing adenoidectomy; divided into three age groups: aged up to 5 years (8 children), 5-10 years (31 children) and over 10 years (15 children). The analyzed material was adenoids removed on the ground of hypertrophy, which caused obstructive symptoms and/or otitis media with effusion onset. Immunohistochemical analyses were carried out using monoclonal mouse antibody (Ab) (Novocastra) directed against human TIMP-1 protein. The presence of TIMP-1 positive lymphocytes within germinal centers and TIMP-1 immunostaining were scored.

Results: The immunohistochemical staining showed the TIMP-1 positive lymphocytes mainly within the mantle zone. There was no statistically significant difference between the mean age of children for TIMP-1 immunoreaction levels. We have not found statistical correlation between the TIMP-1 staining and the clinical status of patients.

Conclusion: It is difficult to interpret our results. Our findings did not demonstrate changes in TIMP-1 expression according to age. This may indicate that the processes of hyperplasia, hypertrophy and atrophy of adenoid are not influenced by age and support our thesis that adenoid involution is rather the effect of changes in the number of lymphoid follicles that changes in them. However there is a need for further observational studies of TIMPs and MMPs in adenoid tissue.
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http://dx.doi.org/10.1016/j.ijporl.2012.11.032DOI Listing
March 2013

IGF-IR in patients with advanced colorectal cancer in correlation with certain clinico-morphological factors: Initial report.

Oncol Lett 2011 Nov 29;2(6):1155-1159. Epub 2011 Aug 29.

Second Department of General and Gastroenterological Surgery, Medical University of Bialystok, Bialystok, Poland.

The insulin-like growth factor (IGF) system comprises two types of peptides (IGF-I and IGF-II), two types of receptors (IGF-IR and IGF-IIR) and six IGF-binding proteins (BP). This system is mainly responsible for the growth and division of cells in the body, regulation of the cell cycle and prevention of apoptosis. The expression of IGF-IR was assessed in the cells of resected primary colorectal tumours in 88 patients (age, 36-87 years; mean 64.78; males, 48 and females, 40) treated surgically at the Second Department of General and Gastroenterological Surgery, Medical University of Bialystok, Poland, in relation to various clinico-morphological factors. The post-operative material was analysed to find the histological type, location of lesions, lymph node involvement staging, distant metastases (pTNM classification), staging in Dukes' classification and the histopathological differentiation grade. The expression of IGF-IR in colorectal cancer cells was assessed using an immunohistochemical method. The findings were subjected to statistical analysis (Chi-square test, multivariation test and Mann-Whitney U test). A positive IGF-IR expression (in at least 10% of cancer cells) was observed in 44 patients. The mean immunoreactive cell count for IGF-IR in all of the tumours studied was 30.79%. The current study showed no correlation of IGF-IR expression in colorectal cancer cells with characteristics such as age and gender of patients, tumour location, type, histological differentiation or histopathological advancement. Immunohistological determination of IGF-IR expression in advanced colorectal cancer cells revealed controversial scores. Evaluation should be confirmed by using other methods and enhanced to include adenomas and early colorectal cancers.
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http://dx.doi.org/10.3892/ol.2011.396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3406542PMC
November 2011

[Gap junction intercellular communication in carcinogenesis of endometrial cancer].

Ginekol Pol 2011 Jul;82(7):520-4

Zakład Patomorfologii Ogólnej Uniwersytetu Medycznego w Białymstoku, Polska.

One of the mechanisms for direct cell to cell signaling is mediated by gap junctions. These junctions are formed by connexins, transmembrane proteins. Gap junction intercellular communication (GJIC) plays a critical role in tissue development, differentiation of cells, and regulation of tissue homeostasis. Cancer cells are characterized by growth and/or differentiation disorders. Endometrial cancer is the most common gynecological malignancy in developed countries. In this study we discuss the putative role of GJIC and adhesion molecules in the development of endometrial cancer The relationships of GJIC to the process of apoptosis and function of some adhesion proteins have also been underlined.
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July 2011

STAT3 and apoptosis regulators: Bak and Bcl-xL in endometrioid adenocarcinomas of different estrogen receptor-α immunoprofile.

Gynecol Endocrinol 2011 Aug;27(8):536-40

Department of Pathology, Maria Sklodowska-Curie Memorial Bialystok Oncology Center and Medical University of Bialystok, Ogrodowa 12, 15-027 Bialystok, Poland.

Estrogen receptor (ER) is a major feature of endometrioid adenocarcinoma. It has a significant impact on constitution of estrogen-responsiveness of this endometrial malignancy, in which STAT3 (signal transducer and activator of transcription) becomes hyperactivated. The aim of our study was to detect immunohistochemically and compare expressions of STAT3 with apoptosis regulators (Bak and Bcl-xL) in regard to different pathological features and variably pronounced ER-α immunoprofile in 78 endometrioid adenocarcinomas. STAT3 was abundantly detected in nuclei of cancer cells in 54 cases, thus pointing at its activation as an universal nuclear transcriptional factor. Bcl-xL and Bak were expressed in cytoplasm of malignant cells in 62 and 20 cancers, respectively. STAT3 correlated both with Bcl-xL (p = 0.001, r = 0.365) and Bak (p  < 0.001, r = 0.436) in all of endometrioid adenocarcinomas and variably in different subgroups of these tumours segregated in regard to grading, staging and patients' age. Remarkably, only ER-α positive cancers retained these correlations in opposition to ER-α negative tumours with negativity defined as an immunoreactivity below 10%. ER-α receptor probably enhances interactions between STAT3 and Bcl-xL to be present in statistically significant manner. Presence of ER-α receptor seems to be crucial for relationships among Bcl-xL and STAT3 to occur in endometrioid adenocarcinomas.
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http://dx.doi.org/10.3109/09513590.2010.507286DOI Listing
August 2011
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