Publications by authors named "Gabor Cserni"

158 Publications

The role of indocyanine green fluorescence in sentinel lymph node biopsy for breast cancer

Orv Hetil 2021 02 21;162(8):293-297. Epub 2021 Feb 21.

1 Bács-Kiskun Megyei Kórház, a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza, Általános Sebészeti Osztály, Kecskemét, Nyíri út 38., 6000.

Összefoglaló. Bevezetés: Napjainkban az őrszemnyirokcsomó felkeresésének legelterjedtebb módszere a radioizotópos és kék festékes kettős jelölés, emellett azonban több más jelölés is alkalmazható. Az indociánzöld-fluoreszcencia ígéretes nyirokút-térképezési módszer, mely a találati arányát tekintve - irodalmi adatok alapján - összevethető a radioizotópos módszerrel. Módszer: Osztályunkon 2020. 03. 31. és 2020. 04. 15. között 10, emlőrák miatt operált betegünknél alkalmaztuk az indociánzöld és a kék festékes kettős jelölés módszerét az őrszemnyirokcsomó felkeresésére. Eredmények: A 10 operált betegünknél összesen 17 őrszemnyirokcsomót azonosítottunk és távolítottunk el. 16 őrszemnyirokcsomó jól festődött indociánzölddel (találati arány: 0,94; 95%-os konfidenciaintervallum [CI ]: 0,73-0,99), míg kék festékkel 9 jelölődött (találati arány: 0,53; 95%-os CI: 0,31-0,74). A szövettani feldolgozás során összesen 2 őrszemnyirokcsomó bizonyult áttétesnek, ezek közül 1 kék és fluoreszcens volt, 1 pedig csak kék festékkel jelölődött. Következtetés: Kezdeti, kis esetszámnál nyert tapasztalataink alapján az indociánzöld jelölés emlőrák során végzett őrszemnyirokcsomó-biopszia esetén jól használható kettős jelölési módszer részeként, kék festékkel kiegészítve. A módszer találati aránya, valamint fals negatív aránya irodalmi adatok alapján nem különbözik szignifikánsan a radioizotópos jelölés módszerétől. Orv Hetil. 2021; 162(8): 293-297.

Summary:

Introduction: The current practice in sentinel lymph node biopsy for breast cancer is the radioisotope and blue dye dual labelling technique, however, other mapping methods are also available. Indocyanine green fluorescence is one of the best alternatives of the standard technique, with detection rates comparable to those of the radioisotope method.

Method: Between 31. 03. 2020 and 15. 04. 2020, a total of 10 sentinel lymph node biopsies for breast cancer were performed using the indocyanine green fluorescence and blue dye dual technique.

Results: 17 sentinel lymph nodes were detected and removed in total, from which 16 showed explicit fluorescence activity (detection rate: 0.94; 95% confidence interval [CI]: 0.73-0.99), whilst 9 where blue (detection rate: 0.53; 95% CI: 0.31-0.74). During histopathological examination, 2 sentinel lymph nodes proved to be metastatic, from which 1 was fluorescent and blue, the other was blue only.

Conclusion: Regarding our early experience based on a small number of patients, indocyanine green fluorescence, used together with blue dye as part of a dual technique, is a usable method for sentinel lymph node mapping. Based on data from the literature, the detection rate and the false-negative rate of the indocyanine green fluorescence method shows no significant difference from the radioisotope mapping technique. Orv Hetil. 2021; 162(8): 293-297.
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http://dx.doi.org/10.1556/650.2021.31994DOI Listing
February 2021

The Added Value of SOX10 Immunohistochemistry to Other Breast Markers in Identifying Cytokeratin 5-Positive Triple Negative Breast Cancers as of Mammary Origin.

Pathobiology 2021 Feb 10:1-6. Epub 2021 Feb 10.

Department of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary.

Aims: Triple-negative breast cancer (TNBC) represents a specific group that lacks the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2 and might also lack the expression other breast markers like GATA3, mammaglobin (MG), GCDFP15 (growth cystic disease fluid protein 15), and NYBR1; when this occurs, proving the breast origin of a metastasis is a challenging task. In the present study, we assessed the added value of SOX10 immunohistochemistry to known GATA3, MG, GCDFP15, and NY-BR-1 statuses in a series of CK5-positive primary TNBCs.

Methods: Tissue microarrays were made from the formalin-fixed and paraffin-embedded blocks of 120 TNBCs, and 3-4-mm-thick sections were immunostained for SOX10. The cut-off for a positive reaction was at least 10% of tumor cells staining.

Results: In our cohort, SOX10 positivity was seen in 82/119 cases, 61, 74, 76, and 82 all of which were GATA3, MG, GCDFP15, and NY-BR-1 negative, respectively. Of the SOX10 negative cases, 12 stained with at least another breast marker. Nevertheless, 25/119 (21%) cases remained negative with all markers assessed.

Discussion: SOX10 proved to be the most commonly positive breast marker in our CK5 expressing TNBCs, but the other markers also had some additive value to SOX10.
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http://dx.doi.org/10.1159/000512006DOI Listing
February 2021

The panel of syntaxin 1 and insulinoma-associated protein 1 outperforms classic neuroendocrine markers in pulmonary neuroendocrine neoplasms.

APMIS 2021 Jan 8. Epub 2021 Jan 8.

Department of Pathology, University of Szeged, Szeged, Hungary.

Syntaxin-1 (STX1) is a recently described highly sensitive and specific neuroendocrine marker. We evaluated the applicability of STX1 as an immunohistochemical marker in pulmonary neuroendocrine neoplasms (NENs). We compared STX1 with established neuroendocrine markers, including insulinoma-associated protein 1 (INSM1). Typical carcinoids (n = 33), atypical carcinoids (n = 7), small cell lung carcinomas ([SCLCs] n = 30), and large cell neuroendocrine lung carcinomas (n = 17) were immunostained using tissue microarray for STX1, chromogranin A, synaptophysin, CD56, and INSM1. Eighty-four of eighty-seven (96.5%) NENs showed STX1 positivity. Carcinoids and LCNECs typically presented a combined strong membranous and weak cytoplasmic staining pattern; cytoplasmic expression was predominately observed in SCLCs. The sensitivity of STX1 was 90% in SCLCs and 100% in typical carcinoids, atypical carcinoids, and large cell neuroendocrine lung carcinomas. The overall sensitivity of STX1 in pulmonary NENs was 96.6%, and the sensitivity of the other markers was as follows: chromogranin A (85.2%), synaptophysin (85.2%), CD56 (92.9%), and INSM1 (97.7%). STX1 was found to be an excellent neuroendocrine marker of pulmonary NENs, with sensitivity and specificity surpassing that of classic markers. We propose a panel of STX1 and INSM1 for the routine immunohistochemical workup of pulmonary NENs.
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http://dx.doi.org/10.1111/apm.13113DOI Listing
January 2021

[Pathological diagnosis, work-up and reporting of breast cancer. Recommendations from the 4th Breast Cancer Consensus Conference].

Magy Onkol 2020 Dec 30;64(4):301-328. Epub 2020 Nov 30.

II. Sz. Patológiai Intézet, Semmelweis Egyetem, Budapest, Hungary.

There have been some relevant changes in the diagnosis and treatment of breast cancer to implement the updating of the 2016 recommendations made during the 3rd national consensus conference on the disease. Following a wide interdisciplinary consultation, the present recommendations have been finalized after their public discussion at the 4th Hungarian Breast Cancer Consensus Conference. The recommendations cover non-operative, intraoperative and postoperative diagnostics, the determination of prognostic and predictive markers and the content of the cytology and histology reports. Furthermore, it touches some special issues such as the current status of multigene molecular markers, the role of pathologists in clinical trials and prerequisites for their involvement, some relevant points about the future. The most important changes include the integration of the TNM 8th edition, the WHO classification of breast tumors 5th edition, the ASCO/CAP HER2 assessment guidelines from 2018, and the Yokohama terminology for cytology reporting; a more detailed text on tumor-infiltrating lymphocytes and size determination after neoadjuvant therapy and a broader discussion of molecular tests.
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December 2020

Mixed Invasive Apocrine Papillary/Micropapillary Carcinoma of the Breast: Another Brick in the Triple-Negative Wall.

Int J Surg Pathol 2020 Sep 10:1066896920954920. Epub 2020 Sep 10.

Santa Chiara Hospital, Trento, Italy.

Pure invasive papillary carcinoma (IPC) is a rare subtype of breast carcinoma with good prognosis compared with classical invasive breast carcinoma (IBC) of no special type. The majority of IPC are estrogen receptor and progesterone receptor (ER/PR) positive and HER2 negative (luminal A-like). We report the case of a 72-year-old women who was referred to the Senology Clinic for a routine workup following surgery for an intraductal papilloma. The core needle biopsy (CNB) showed a lesion mainly composed of irregular papillae and micropapillae with apocrine epithelial cells of low-to-intermediate nuclear grade, without a myoepithelial cell layer within the papillae and at the periphery, as demonstrated with multiple immunostains. The diagnosis of apocrine papillary lesion of uncertain malignant potential was made. The subsequent lumpectomy showed an IBC with the same cyto-architectural features as the CNB. In addition, lymphovascular invasion and papillary/micropapillary apocrine in situ lesion were noted. Notably, the tumor was ER/PR and HER2 negative and strongly positive for androgen receptor. A final diagnosis of mixed apocrine papillary/micropapillary carcinoma with triple-negative status was made. To the best of our knowledge, this is the first report of an IBC with these features. Breast pathologists should be aware of this entity when dealing with CNB samples characterized by a complex papillary lesion with apocrine atypia that lacks a myoepithelial cell layer on multiple immunostains. These lesions should be classified at least as of uncertain malignant potential based on the cyto-architectural features prompting a surgery for removal.
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http://dx.doi.org/10.1177/1066896920954920DOI Listing
September 2020

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study.

Breast Cancer Res Treat 2020 Oct 30;183(3):759-770. Epub 2020 Jul 30.

Department of Pathology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Purpose: For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk.

Methods: Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff's alpha (KA) and Gwet's AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression.

Results: Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05-6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35-5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34-10.23) were independently associated with a higher iIBC risk.

Conclusions: Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.
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http://dx.doi.org/10.1007/s10549-020-05816-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497690PMC
October 2020

Examination of Tumor Regression Grading Systems in Breast Cancer Patients Who Received Neoadjuvant Therapy.

Pathol Oncol Res 2020 Oct 20;26(4):2747-2754. Epub 2020 Jul 20.

Department of Pathology, Faculty of Medicine, University of Szeged, Állomás u. 1., Szeged, 6725, Hungary.

Neoadjuvant therapy is a common form of treatment in locally advanced breast cancer (LABC) patients. Besides some guidelines for grading regression, a standardized general scheme is not yet available. The aim of our study was to compare the prognostic impact of different regression grading systems, namely the TR/NR, Chevallier, Sataloff, Denkert-Sinn, Miller-Payne, NSABP-B18, Residual Disease in Breast and Nodes and Residual Cancer Burden (RCB) on disease-free (DFS) and overall survival (OS). Data of 746 breast cancer patients treated in neoadjuvant setting between 1999 and 2019 have been included. The different regression grades and follow-up data were collected from medical charts. Statistical analysis included the Kaplan-Meier method, log-rank test and multivariate Cox regression. The average patient age was 55 years. The DFS and OS estimates of patients with complete pathological regression and residual in situ carcinoma have been significantly more favorable than those having partial regression or no signs of regression (pDFS<0.001, pOS < 0.001). Significant differences were found between DFS estimates of classes with partial regression and without regression defined by RCB. Concerning DFS estimates, the RCB classification (p = 0.019), while regarding OS data the y-stage (p = 0.011) and the nodal status (ypN; p = 0.045) were significant prognosticators by multivariate Cox regression. Regression grading systems help the evaluation of regression in LABC patients treated with neoadjuvant therapy. Of the several grading systems compared, the RCB classification makes the best distinction between the outcomes of the different classes, therefore we recommend the inclusion of RCB into the histopathological findings.
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http://dx.doi.org/10.1007/s12253-020-00867-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471177PMC
October 2020

A Clinicopathological Approach to Odontogenic Cysts: the Role of Cytokeratin 17 and bcl2 Immunohistochemistry in Identifying Odontogenic Keratocysts.

Pathol Oncol Res 2020 Oct 6;26(4):2613-2620. Epub 2020 Jul 6.

Department of Pathology, University of Szeged, Állomás u. 1, Szeged, H-6725, Hungary.

Odontogenic keratocysts (OKCs) are developmental cysts of the jaws that require proper diagnosis due to their potential for local aggressive growth and recurrences. OKCs have a typical parakeratotic epithelium demonstrating transepithelial cytokeratin 17 (CK17) and basal bcl2 staining on immunohistochemistry (IHC), which distinguishes them from other common jaw cysts. Secondary to inflammation, the epithelial lining may be altered and loses the typical IHC phenotype. The aim of the present study was to analyse a series of consecutive jaw cysts for their expression of CK17 and bcl2 and assess how these IHC stains may help in their diagnosis. All cysts were retrospectively assessed for available clinical, radiological and pathological findings and diagnoses were revised whenever needed. 85 cysts from 72 patients were collected from two departments. The series had 21 OKCs, the remaining non-OKCs included radicular/residual, dentigerous, paradental, lateral periodontal, botryoid odontogenic cysts. OKCs with typical epithelium showed the typical IHC phenotype, which was generally lost in inflammation-associated altered epithelium. Contrarily to earlier descriptions, a wide variety of CK17 positivity was seen in the majority of non-OKCs, including focal transepithelial staining. Basal bcl2 staining was also seen in 16 non-OKCs. These stainings were never as strong in intensity as seen in OKCs. One case was histopathologically identified as OKC due to focally maintained IHC profile. CK17 and bcl2 IHC may help in the diagnosis of OKCs, but must be interpreted with caution and is not a yes or no tool in the diagnostic puzzle.
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http://dx.doi.org/10.1007/s12253-020-00866-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471163PMC
October 2020

Az első száz minimálisan invazív tüdőlebeny-eltávolítás eredményei osztályunk beteganyagában.

Magy Seb 2020 Jun;73(2):57-60

Sebészeti Osztály,Bács-Kiskun megyei Kórház, Bács-Kiskun megyei Kórház, Sebészeti Osztály, 6000 Kecskemét, Nyíri út 38.

Patients And Methods: Between 1st November 2013 and 30th June 2019 we performed 112 VATS lobectomies with isolated intubation and anterior approach. In 98 cases lobectomies were performed for malignant lesions, while in 9 cases for benign changes. 78 men and 34 women were operated on. The average age was 60.5 years (42-63). In 5 cases the left upper lobes were resected, in cases 36 the left lower lobes, in 15 cases the right upper lobes, in 11 cases the mid lobes, in 44 cases the right lower lobes, and in one case pneumonectomy was performed.

Results: there was no postoperative mortality. Conversion was required in three 3 patients. The average time of surgery was 150 minutes (70-215). Re-operation was needed in two cases due to bleeding and air leakage. Out of the 112 operations, primary lung cancer was demonstrated on pathology in 88 cases, while benign lesions /inflammation in 9 cases. The stages of primary lung cancer were the following: I.a:57, I.b:22, II.a:6, II.b:3 patients. Tumour subtypes were the detailed as 52 adenocarcinoma, 23 squamous cell cc., 2 small cell cc., 5 large cell cc., and 6 carcinoid. 10 patients underwent VATS lobectomy for metastatic disease.

Conclusion: As a result of an adequate learning period, VATS lobectomies have become a routine surgery in our unit. Currently 65% of the thoracotomies and more than 50 percent of the lobectomies are performed by the VATS method. Our results are comparable to national as well as international data.
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http://dx.doi.org/10.1556/1046.73.2020.2.2DOI Listing
June 2020

Comparison of Nottingham Prognostic Index, PREDICT and PrognosTILs in Triple Negative Breast Cancer -a Retrospective Cohort Study.

Pathol Oncol Res 2020 Oct 20;26(4):2443-2450. Epub 2020 Jun 20.

Faculty of Medicine, Department of Pathology, University of Szeged, Állomás u. 1, Szeged, 6725, Hungary.

Triple-negative breast cancer (TNBC) represents a heterogenous subtype of breast cancer with generally poor prognosis. The prediction of its prognosis remains essential to clinicians in their therapeutical decision-making process. The aim of our study was to compare the validity of three multivariable analysis derived prognostic systems, the Nottingham Prognostic Index (NPI), PREDICT and PrognosTILs (a prognosticator including tumor infiltrating lymphocytes, TILs) in a series of TNBCs. Patients operated on with TNBC at the Department of Surgery, Bács-Kiskun County Teaching Hospital, Kecskemét between 2005 and 2016 were included. Clinical and pathological parameters and follow-up data were collected from medical charts. TILs were assessed retrospectively, following international recommendations. Estimated survivals of PrognosTILs, PREDICT and NPI were recorded and compared with real outcomes. Altogether 136 patients were included in this retrospective study. In univariate Cox analysis, type of surgery, pT, pN, stage, NPI and type of adjuvant therapy were the significant prognostic variables. The multivariate Cox-regression strengthened that NPI is an independent predictor of overall and disease-free survivals in TNBCs. The NPI, PREDICT and PrognosTILs could be compared directly only in a ROC curve analysis: the sensitivities and specificities of these predicting systems are rather similar with area under the curve values falling between 0.7 and 0.8, and NPI having the highest values. Our findings reflect the diverse prognosis of TNBC and highlight the difficulties of predicting its outcome. None of the three multivariable prognosticators is inferior to the others, the NPI can reliably be used for TNBCs.
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http://dx.doi.org/10.1007/s12253-020-00846-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471141PMC
October 2020

Architectural Grade Combined With Spread Through Air Spaces (STAS) Predicts Recurrence and is Suitable for Stratifying Patients Who Might Be Eligible for Lung Sparing Surgery for Stage I Adenocarcinomas.

Pathol Oncol Res 2020 Oct 20;26(4):2451-2458. Epub 2020 Jun 20.

Department of Surgery, University of Szeged, Semmelweis u. 8., Szeged, H6720, Hungary.

The spread through air spaces (STAS) has a main role in local recurrence of stage I lung adenocarcinomas (LAs), therefore its presence might question sublobar resection as a therapeutic option. The aim of our study was to evaluate the distribution of STAS in stage I LAs, to stratify patients according to local recurrence and to identify a group of patients who might be suitable for sublobar surgery. Patients resected with LA were included. The presence of STAS was recorded on hematoxylin eosin stained slides and clinicopathological data were obtained from medical charts. Overall survival (OS) and disease-free survival (DFS) were registered. Statistical methods included Kruskal-Wallis tests, Kaplan-Meier analyses, log-rank tests and Cox-regressions. 292 patients were included. STAS was identified in 38.7% and 95.7% of micropapillary carcinomas showed STAS. Significant correlation was found between STAS and high-grade patterns. Significant differences were found between OS and DFS estimates of STAS0 and STAS1 cases (5-y-OS: 80.0% vs. 68.4%; 5-y-DFS: 71.1% vs. 57.1%). The presence of STAS was associated with unfavorable prognosis in low and intermediate architectural grades, but not in high-grade. Multivariate analysis revealed that architectural grade (HR:2.09; HR:1.52) and STAS (HR:1.51; HR:1.48) were independent prognostic markers in stage I LA. Architectural grade combined with STAS was superior to other prognostic grades. The combination of architectural grade and STAS proved to be a prognostic factor that is superior to previously introduced grading systems. Patients having low and intermediate grade LAs without STAS might be eligible for sublobar resection.
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http://dx.doi.org/10.1007/s12253-020-00855-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471099PMC
October 2020

Histological type and typing of breast carcinomas and the WHO classification changes over time.

Authors:
Gábor Cserni

Pathologica 2020 Mar;112(1):25-41

Bács-Kiskun County Teaching Hospital, Department of Pathology, Kecskemét, Hungary.

The World Health Organization's new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast carcinomas which is still principally based on histological features and follows the traditions of histological typing. It gives a subjective and critical view on the WHO classifications and their changes over time, and describes the changes related to some of the most common or challenging breast carcinomas: in situ carcinomas, invasive breast carcinomas of no special type, lobular, cribriform, tubular, mucinous, papillary, metaplastic carcinomas and carcinomas with medullary pattern and those with apocrine differentiation are discussed in more details. Although the 5 edition of the classification is not perfect, it has advantages which are mentioned along with problematic issues of classifications.
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http://dx.doi.org/10.32074/1591-951X-1-20DOI Listing
March 2020

[Laparoscopic and open complete mesocolic excision in right-sided colon cancer compared with open and laparoscopic surgery].

Magy Seb 2020 Mar;73(1):23-28

Sebészeti Osztály, Bács-Kiskun Megyei Kórház 6000 Kecskemét, Nyíri u 38.

In 2009, Hohenberger translated the concept of total mesorectal excision to colon cancer surgery and he named it complete mesocolic excision (CME). The principle of CME is based on wide mesenteric excision in the embriologic plane to remove mesenteric lymph nodes, central vascular ligation without damage of the peritoneal layer. CME can be performed by laparoscopic and open methods. To make sure that we are capable of performing right laparoscopic hemicolectomy with similar results to the open method. A cohort of 156 consecutive patients were operated on with malignant right-sided colon tumours from 01.09.2016 to 30.06.2019. 143 curative resections were performed in 63 men and 80 women. The average age of men and women were 71.5 and 72.75 years, respectively. 84 laparoscopic and 59 open operations were performed. 84 patients underwent CME surgery and 56 conventional resections. The average length of the specimen was 22.34 cm in the conventional and 24.97 cm in CME surgery ( = 0.18) and the average lymph node number were 15.4 and 16.9, respectively ( = 0.24). The average duration of the operation was 111 minutes for the conventional and 136 minutes for the CME group ( = 0.0014), while the average length of stay were 7.47 days and 5.65 days ( = 0.0004) respectively for the cases without complications. We are yet in the learning period, but based on the early results, it might be concluded that the operation can be performed by laparoscopic methods as well with similar results to the open operation but with shorter length of stay.
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http://dx.doi.org/10.1556/1046.73.2020.1.3DOI Listing
March 2020

[The importance of the extracapsular extension of the sentinel node metastasis in the surgical treatment of breast cancer].

Magy Seb 2020 03;73(1):16-22

Általános Patológiai Osztály, Bács-Kiskun Megyei Kórház, a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktatókórháza Kecskemét.

Introduction: The introduction of sentinel node biopsy (SNB) has led to a significant decrease of axillary lymph node dissections (ALND). The importance of the extracapsular extension (ECE) in the sentinel lymph node (SN) remains unclear. Method: The data of 635 patients with T1-T2N0M0 invasive breast cancer who underwent SNB between 2014 and 2018 were retrospectively analysed. 25% of the SNB patients (158) had metastasis in the SNs. These patients were grouped based on the presence or absence of ECE. The main objective of our study was to analyse the occurrence of massive (>3) node metastasis in the case of ECE negative and ECE positive patients, where ALND was performed. Results: There were 91/158 patients (58%) in the ECE negative group and 67/158 patients (42%) in the ECE positive group. ALND was performed in 42% of the ECE negative and in 69% of the ECE positive patients. There were no significant differences in the mean age of the patients; size, histological type and grade of the tumours, presence of lymphovascular invasion and proportion of hormone and HER2 receptor positivities. In the ECE negative ALND group, pN1 involvement was 82%, pN2+pN3 involvement represented 18% of cases. In the ECE positive ALND group, pN1 involvement was 60%, pN2+pN3 involvement was found in 40% of cases. The presence of ECE was associated with greater axillary disease burden. These results show a significant difference ( = 0.038). Conclusions: ECE of the SN is an important predictor for non-sentinel lymph node involvement. These data suggest, when ECE is confirmed, it is a further factor to be considered in deciding about ALND.
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http://dx.doi.org/10.1556/1046.73.2020.1.2DOI Listing
March 2020

[Large-cell neuroendocrine carcinoma of the lung - challenges of diagnosis and treatment].

Orv Hetil 2020 Feb;161(8):313-319

Csongrád Megyei Mellkasi Betegségek Szakkórháza Deszk.

Small-cell lung carcinoma (SCLC) and the rare large-cell neuroendocrine carcinoma belong to the high grade pulmonary neuroendocrine carcinomas. Making the correct diagnosis and selection of treatment modalities require multidisciplinary meetings due to the morphological overlaps, aggressive behaviour and debated therapeutic guidelines of these entities. A 52-year-old woman was admitted to the hospital because of headache, nausea and tenebrous vision. The CT revealed metastatic tumour mass in the occipital lobe and in the cerebellum. Both tumours were removed and resulted in histological diagnosis of metastatic neuroendocrine carcinoma. Chest X-ray established contrast-enhancing lesion in the left lung. Bronchoscopy was performed and histological examination revealed large-cell neuroendocrine carcinoma. Postoperative skull irradiation and small-cell lung cancer chemotherapy protocol were utilized. Due to atelectasis and progression, chest irradiation was initiated, which was interrupted because of novel brain metastases. Further chemotherapy followed the non-small-cell lung cancer protocol. After 3 months, thoracic progression, brain and disseminated bone metastases were diagnosed. After a 14-month-long therapy, the patient deceased. Large-cell neuroendocrine carcinoma has a poor prognosis, the incidence of brain metastasis is 25-50%. In early stage large-cell neuroendocrine carcinoma, lobectomy is the standard treatment and adjuvant chemotherapy should also be considered. Although the non-small-cell lung cancer chemotherapy protocol is approved widely in the treatment of large-cell neuroendocrine carcinoma, the utility of SCLC scheme has also been suggested. Orv Hetil. 2020; 161(8): 313-319.
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http://dx.doi.org/10.1556/650.2020.31581DOI Listing
February 2020

Grading Ductal Carcinoma In Situ (DCIS) of the Breast - What's Wrong with It?

Pathol Oncol Res 2020 Apr 27;26(2):665-671. Epub 2019 Nov 27.

Department of Pathology, University of Szeged, Állomás u. 1, Szeged, H-6725, Hungary.

Ductal carcinoma in situ of the breast is a non-obligate precursor of invasive breast cancer, and at its lower risk end might not need treatment, a hypothesis tested in several currently running randomized clinical trials. This review describes the heterogeneity of grading ductal carcinoma in situ (DCIS). First it considers differences between low and high grade DCIS, and then it looks at several grading schemes and highlights how different these are, not only in the features considered for defining a given grade but also in their wording of a given variable seen in the grade in question. Rather than being fully comprehensive, the review aims to illustrate the inconsistencies. Reproducibility studies on grading mostly suggestive of moderate agreement on DCIS differentiation are also illustrated. The need for a well structured, more uniform and widely accepted language for grading DCIS is urged to avoid misunderstanding based misclassifications and improper treatment selection.
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http://dx.doi.org/10.1007/s12253-019-00760-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242244PMC
April 2020

Immunohistochemical Characterization of Reactive Epithelial Changes in Odontogenic Keratocysts.

Pathol Oncol Res 2020 Jul 18;26(3):1717-1724. Epub 2019 Oct 18.

Department of Prosthodontics, Faculty of Dentistry, University of Szeged, Tisza Lajos krt 64-66., Szeged, H-6720, Hungary.

Odontogenic keratocysts (OKCs) have a diagnostic thin epithelial lining characterised by a linear epithelial connective tissue interface generally lacking inflammatory changes, basal palisading of the nuclei and a wavy parakeratotic layer on the surface. This typical epithelium may convert to a thicker non-keratinizing one with rete pegs and a relatively flat surface after operative decompression. The aim was to characterize this type of epithelial change by immunohistochemistry for bcl2, keratin17, 10 and 19. Eleven out of 33 archived OKCs demonstrated an altered epithelium related to previous biopsy, decompressing drainage or inflammation. The typical basal bcl2 staining was lost in 10/11 cases; transepithelial CK17 was lost or markedly reduced in 9/11 cases. CK10 displayed a segmental upper layer staining in OKCs, and its loss or partial loss in the altered epithelium did not differ from negative areas of OKCs. CK19 displayed various staining patterns in the altered epithelium from lost to maintained in a patchy transepithelial distribution, the latter of which did not differ from the typical OKC staining pattern. Three of four non-keratinizing epithelial linings with basal palisading displayed immunostaining reminiscent of typical OKC epithelium. The lack of a typical epithelium is not sufficient to exclude the diagnosis of OKC if the sampling is not generous (e.g. biopsy), and the presence of non-keratinizing epithelium with basal palisading and an immunophenotype characteristic of OKC (basal bcl2, patchy or diffuse CK17 and upper layer CK10 positivity) may be consistent with the OKC diagnosis even in the absence of typical epithelial lining.
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http://dx.doi.org/10.1007/s12253-019-00749-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297854PMC
July 2020

Spontaneous pathological complete regression of high-grade triple-negative breast cancer with axillary metastasis.

Pol J Pathol 2019 ;70(2):139-143

Laboratory of Tumour Pathology and Molecular Diagnostics, Szeged, Hungary.

We report on a breast carcinoma with medullary features diagnosed by core needle biopsy in a 72-year-old woman. Both the primary tumour and its fine needle aspiration-proven, rapidly growing axillary metastasis regressed completely in less than 2 months, by the time surgery was performed. The biopsy of the primary tumour demonstrated a dense stromal infiltrate of CD8+/granzyme B+ activated cytotoxic T-cells suggestive of a robust antitumour immune response. Paradoxically, both tumour cells and tumour infiltrating immune cells demonstrated a diffuse PD-L1 expression, revealing that antitumour immune response has the ability to spontaneously overcome inhibitory mechanisms induced by cancerous growth.
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http://dx.doi.org/10.5114/pjp.2019.87105DOI Listing
October 2019

Negative pressure wound therapy of Corynebacterium jeikeium associated granulomatous mastitis.

Breast J 2020 03 11;26(3):508-510. Epub 2019 Sep 11.

Department of Pathology, Bács-Kiskun County Hospital, Kecskemét, Hungary.

We present the first Corynebacterium associated therapy resistant granulomatous mastitis successfully treated with negative pressure wound therapy (NPWT). Our patient had received five different courses of antibiotic therapy, and three surgical explorations before NPWT was introduced and resulted in healing. For a successful treatment, the use of targeted antibiotic therapy, steroid therapy and in case of progressive disease, wide excision is required. When this results in a large wound cavity, NPWT seems an effective and innovative option.
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http://dx.doi.org/10.1111/tbj.13573DOI Listing
March 2020

Selective Heart Irradiation Induces Cardiac Overexpression of the Pro-hypertrophic miR-212.

Front Oncol 2019 16;9:598. Epub 2019 Jul 16.

Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hanover Medical School, Hanover, Germany.

A deleterious, late-onset side effect of thoracic radiotherapy is the development of radiation-induced heart disease (RIHD). It covers a spectrum of cardiac pathology including also heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction. MicroRNA-212 (miR-212) is a crucial regulator of pathologic LVH via FOXO3-mediated pathways in pressure-overload-induced heart failure. We aimed to investigate whether miR-212 and its selected hypertrophy-associated targets play a role in the development of RIHD. RIHD was induced by selective heart irradiation (50 Gy) in a clinically relevant rat model. One, three, and nineteen weeks after selective heart irradiation, transthoracic echocardiography was performed to monitor cardiac morphology and function. Cardiomyocyte hypertrophy and fibrosis were assessed by histology at week 19. qRT-PCR was performed to measure the gene expression changes of miR-212 and forkhead box O3 (FOXO3) in all follow-up time points. The cardiac transcript level of other selected hypertrophy-associated targets of miR-212 including extracellular signal-regulated kinase 2 (ERK2), myocyte enhancer factor 2a (MEF2a), AMP-activated protein kinase, (AMPK), heat shock protein 40 (HSP40), sirtuin 1, (SIRT1), calcineurin A-alpha and phosphatase and tensin homolog (PTEN) were also measured at week 19. Cardiac expression of FOXO3 and phospho-FOXO3 were investigated at the protein level by Western blot at week 19. In RIHD, diastolic dysfunction was present at every time point. Septal hypertrophy developed at week 3 and a marked LVH with interstitial fibrosis developed at week 19 in the irradiated hearts. In RIHD, cardiac miR-212 was overexpressed at week 3 and 19, and FOXO3 was repressed at the mRNA level only at week 19. In contrast, the total FOXO3 protein level failed to decrease in response to heart irradiation at week 19. Other selected hypertrophy-associated target genes failed to change at the mRNA level in RIHD at week 19. LVH in RIHD was associated with cardiac overexpression of miR-212. However, miR-212 seems to play a role in the development of LVH via FOXO3-independent mechanisms in RIHD. As a central regulator of pathologic remodeling, miR-212 might become a novel target for RIHD-induced LVH and heart failure.
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http://dx.doi.org/10.3389/fonc.2019.00598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646706PMC
July 2019

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature.

Eur J Surg Oncol 2019 Dec 5;45(12):2279-2286. Epub 2019 Jul 5.

Department of Histopathology, St. Vincent's University Hospital, Dublin, and School of Medicine, University College, Dublin, Ireland. Electronic address:

Background: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated.

Aim: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature.

Methods: A multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed.

Results: A total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274).

Conclusions: The data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.
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http://dx.doi.org/10.1016/j.ejso.2019.07.011DOI Listing
December 2019

Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer.

Acta Oncol 2019 Nov 4;58(11):1603-1611. Epub 2019 Jul 4.

2nd Department of Pathology, SE-NAP Brain Metastasis Research Group, Semmelweis University, Budapest, Hungary.

Chemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes. It is not known, however, whether treatment with various chemotherapeutic agents with different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in residual cancer. One hundred and twenty breast carcinoma cases with residual disease that were treated with one of three types of pre-operative chemotherapy regimens were selected for the study. The percentage of StrTIL was evaluated in pretreatment core biopsies (pre-StrTIL) and post-treatment surgical tumor samples (post-StrTIL). TIL changes (ΔStrTIL) were calculated from the difference between post-StrTIL and pre-StrTIL. When analyzing the pre-StrTIL and post-StrTIL among the three treatment groups, we detected significant StrTIL increase independently of the treatment applied. Based on distant metastases-free survival analysis, both post-StrTIL and ΔStrTIL was found to be independent prognostic factor in HR negative cases. Significant increase of StrTIL in the residual disease was observed in patients treated with the highly (platinum), moderately (cyclophosphamide) and marginally mutagenic chemotherapeutic agents (taxane, anthracycline). Increase in StrTIL in residual cancer compared to pretreatment tumor tissue is associated with improved distant metastasis-free survival in cases with HR negative breast carcinoma.
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http://dx.doi.org/10.1080/0284186X.2019.1633015DOI Listing
November 2019

[Evaluation of resection margins following breast conserving surgery for breast cancer. ].

Orv Hetil 2019 Jun;160(26):1036-1044

Patológiai Intézet, Szegedi Tudományegyetem, Általános Orvostudományi Kar Szeged.

Breast conserving surgery for breast cancer requires the analysis of surgical margins. If the tumor is not removed completely, additional treatments (reoperation, boost irradiation) are generally recommended. To analyze the information content of histopathology reports on surgical margins in consecutive cases of breast conservation for invasive female breast cancer, to evaluate the frequency of incompletely removed tumors and to estimate the rate of further treatments after incomplete removal. Analysis of margin related data of consecutive histopathology reports from 8 Hungarian pathology units with locoregional treatment related data in case of unsafe margins. 386 reports were analyzed after exclusions. 200 and 32 cases were identified as having unsafe margins according to the previous (<5 mm) and the new (0 mm) definition of unclear margin, respectively. Unsafe margins were more common with lobular carcinomas. Specimens with clear margins weighed more. Reoperations for unsafe margins were performed in 43/180 and 12/22 cases according to the previous and the new definitions, respectively. Only 75/137 patients without reoperation received boost irradiation of the tumor bed; information on boost radiotherapy was often missing. Residual cancer was identified in 15/43 reoperated patients, of whom 9 had >0 mm margin distance. Some pathology reports lack information on surgical margins. Unsafe margin rates decreased with the new definition. Residual cancer may be left behind in case of clear margins with no ink on tumor. Neither reoperation, nor boost radiotherapy is given to some patients with unclear surgical margins. Orv Hetil. 2019; 160(26): 1036-1044.
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http://dx.doi.org/10.1556/650.2019.31449DOI Listing
June 2019

Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212.

Sci Rep 2019 02 4;9(1):1302. Epub 2019 Feb 4.

Metabolic Diseases and Cell Signaling Group, Department of Biochemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary.

Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. MicroRNA-212 (miR-212) has been demonstrated previously to be a crucial regulator of pathologic LVH in pressure-overload-induced heart failure via regulating the forkhead box O3 (FOXO3)/calcineurin/nuclear factor of activated T-cells (NFAT) pathway. Here we aimed to investigate whether miR-212 and its hypertrophy-associated targets including FOXO3, extracellular signal-regulated kinase 2 (ERK2), and AMP-activated protein kinase (AMPK) play a role in the development of HFpEF in CKD. CKD was induced by 5/6 nephrectomy in male Wistar rats. Echocardiography and histology revealed LVH, fibrosis, preserved systolic function, and diastolic dysfunction in the CKD group as compared to sham-operated animals eight and/or nine weeks later. Left ventricular miR-212 was significantly overexpressed in CKD. However, expressions of FOXO3, AMPK, and ERK2 failed to change significantly at the mRNA or protein level. The protein kinase B (AKT)/FOXO3 and AKT/mammalian target of rapamycin (mTOR) pathways are also proposed regulators of LVH induced by pressure-overload. Interestingly, phospho-AKT/total-AKT ratio was increased in CKD without significantly affecting phosphorylation of FOXO3 or mTOR. In summary, cardiac overexpression of miR-212 in CKD failed to affect its previously implicated hypertrophy-associated downstream targets. Thus, the molecular mechanism of the development of LVH in CKD seems to be independent of the FOXO3, ERK1/2, AMPK, and AKT/mTOR-mediated pathways indicating unique features in this form of LVH.
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http://dx.doi.org/10.1038/s41598-018-37690-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362219PMC
February 2019

Patterns of Regression in Breast Cancer after Primary Systemic Treatment.

Pathol Oncol Res 2019 Jul 27;25(3):1153-1161. Epub 2018 Nov 27.

Department of Pathology, Faculty of Medicine, University of Szeged, Állomás u. 1., Szeged, 6725, Hungary.

Despite national guidelines, the evaluation of effects of primary systemic treatment (PST) in breast cancer is a complex challenge. Our aims were to evaluate the response patterns focusing on correlations of radiological and pathological tumor size, regression heterogeneity in different molecular subtypes, cellularity changes and the incidence of enlarged, multinucleated neoplastic cells related to therapy. Slides of pretreatment biopsies and resection specimens of consecutive cases were reevaluated focusing on heterogeneity of regression per whole slide, and 40x or 100x magnification fields. Alteration in cellularity and the presence of multinucleated tumor giant cells were noted. The correlation of pathological and radiological sizes and their alterations were analyzed by Spearman rank correlation. The present study included 106 tumors. A decrease in size (84.9%) and cellularity (76.4%) was noted in all molecular subtypes. Inhomogeneous regression was found in 45.3%, with minor inhomogeneity in the majority. Scatter pattern regression was seen only in 8 cases (7.5%). Significant correlations were found between the pathological and radiological sizes (p = 0.02), and between the alterations of cellularity and pathological and radiological size (p = 0.04; p = 0.03, respectively). Multinucleated tumor giant cells were noted in 17.9% (n = 19), nearly exclusively in cases treated with PST including taxanes. Regression inhomogeneity following PST is present in about half of the cases, and is not related to molecular subtypes. The evaluation of the maximum area of the tumor bed is recommended for the proper evaluation of regression. Multinucleated tumor giant cells are related to PST including taxane derivate, and may cause upgrading.
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http://dx.doi.org/10.1007/s12253-018-0557-7DOI Listing
July 2019

Apocrine Encapsulated Papillary Carcinoma of the Breast: The First Reported Case with an Infiltrative Component.

J Breast Cancer 2018 Jun 20;21(2):227-230. Epub 2018 Jun 20.

Department of Pathology, University of Szeged, Szeged, Hungary.

Apocrine encapsulated papillary carcinoma (EPC) of the breast is a rare neoplasm, and only 10 cases have been reported in the literature to date. Although EPC by definition lacks a peripheral myoepithelial layer, all previously published apocrine EPC cases were clinically indolent and lacked a conventional invasive component. Herein, we report the 11th case of apocrine EPC, which had a conventional invasive carcinoma component and provides evidence of the malignant potential of this entity. We postulate that apocrine EPC is most likely a morphological variant of conventional EPC, with the same unpredictable malignant potential as non-apocrine cases.
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http://dx.doi.org/10.4048/jbc.2018.21.2.227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015972PMC
June 2018

Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer.

J Pathol Clin Res 2018 10 23;4(4):241-249. Epub 2018 Aug 23.

Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.

Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan-Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease-free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.
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http://dx.doi.org/10.1002/cjp2.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174618PMC
October 2018

Expression of growth hormone-releasing hormone receptors in apocrine adnexal tumours and apocrine glands of the skin.

Pol J Pathol 2018;69(1):48-52

Encouraged by our previous finding of growth hormone-releasing hormone receptor (GHRH-R) expression in metaplastic and neoplastic apocrine breast epithelium, we examined a small series of skin adnexal tumours with various degrees of apocrine (oxyphilic) differentiation, as well as normal axillary and anogenital apocrine sweat glands, for the expression of GHRH-R. Sections of formalin-fixed paraffin-embedded tissue blocks were immunostained for gross cystic disease fluid protein-15 (GCDFP-15) and androgen receptor (AR), to prove apocrine differentiation and correlate it with areas of GHRH-R expression. All but one of 19 tumours with apocrine epithelium and all five benign apocrine glands stained with both anti-GHRH-R antibodies used, each labelling a different domain of the receptor. Non-apocrine areas of the tumours and four eccrine tumours without oxyphilic features did not stain, but most sebaceous glands and some eccrine glands were labelled. Our data suggest that anti-GHRH-R antibodies highlight apocrine differentiation at extramammary sites also. Although GHRH-R seems to have a sensitivity comparable to classic apocrine markers such as AR and GCDFP-15, it seems to be inferior in specificity. The GHRH-R labelling of apocrine glands and neoplastic epithelium might also interfere with the emerging anti-GHRH targeted treatment of some malignancies acting on these receptors.
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http://dx.doi.org/10.5114/pjp.2018.75336DOI Listing
July 2018

Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study.

Breast Cancer Res Treat 2018 Aug 17;171(1):1-9. Epub 2018 May 17.

Discipline of Pathology, National University of Ireland, Galway, Ireland.

Background: Several studies have demonstrated a prognostic role for stromal tumour infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC). The reproducibility of scoring sTILs is variable with potentially excellent concordance being achievable using a software tool. We examined agreement between breast pathologists across Europe scoring sTILs on H&E-stained sections without software, an approach that is easily applied in clinical practice. The association between sTILs and response to anthracycline-taxane NACT was also examined.

Methodology: Pathologists from the European Working Group for Breast Screening Pathology scored sTILs in 84 slides from 75 TNBCs using the immune-oncology biomarker working group guidance in two circulations. There were 16 participants in the first and 19 in the second circulation.

Results: Moderate agreement was achieved for absolute sTILs scores (intraclass correlation coefficient (ICC) = 0.683, 95% CI 0.601-0.767, p-value < 0.001). Agreement was less when a 25% threshold was used (ICC 0.509, 95% CI 0.416-0.614, p-value < 0.001) and for lymphocyte predominant breast cancer (LPBC) (ICC 0.504, 95% CI 0.412-0.610, p-value < 0.001). Intra-observer agreement was strong for absolute sTIL values (Spearman ρ = 0.727); fair for sTILs ≥ 25% (κ = 0.53) and for LPBC (κ = 0.49), but poor for sTILs as 10% increments (κ = 0.24). Increasing sTILs was significantly associated with an increased likelihood of a pathological complete response (pCR) on multivariable analysis.

Conclusion: Increasing sTILs in TNBCs improves the likelihood of a pCR. However, inter-observer agreement is such that H&E-based assessment is not sufficiently reproducible for clinical application. Other methodologies should be explored, but may be at the cost of ease of application.
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http://dx.doi.org/10.1007/s10549-018-4825-8DOI Listing
August 2018