Publications by authors named "Anna Farnedi"

22 Publications

  • Page 1 of 1

Proteoglycan-based diversification of disease outcome in head and neck cancer patients identifies NG2/CSPG4 and syndecan-2 as unique relapse and overall survival predicting factors.

BMC Cancer 2015 May 3;15:352. Epub 2015 May 3.

COMT - Centre for Molecular Translational Oncology & Department of Life Sciences, University of Parma, Parma, Italy.

Background: Tumour relapse is recognized to be the prime fatal burden in patients affected by head and neck squamous cell carcinoma (HNSCC), but no discrete molecular trait has yet been identified to make reliable early predictions of tumour recurrence. Expression of cell surface proteoglycans (PGs) is frequently altered in carcinomas and several of them are gradually emerging as key prognostic factors.

Methods: A PG expression analysis at both mRNA and protein level, was pursued on primary lesions derived from 173 HNSCC patients from whom full clinical history and 2 years post-surgical follow-up was accessible. Gene and protein expression data were correlated with clinical traits and previously proposed tumour relapse markers to stratify high-risk patient subgroups.

Results: HNSCC lesions were indeed found to exhibit a widely aberrant PG expression pattern characterized by a variable expression of all PGs and a characteristic de novo transcription/translation of GPC2, GPC5 and NG2/CSPG4 respectively in 36%, 72% and 71% on 119 cases. Importantly, expression of NG2/CSPG4, on neoplastic cells and in the intralesional stroma (Hazard Ratio [HR], 6.76, p = 0.017) was strongly associated with loco-regional relapse, whereas stromal enrichment of SDC2 (HR, 7.652, p = 0.007) was independently tied to lymphnodal infiltration and disease-related death. Conversely, down-regulated SDC1 transcript (HR, 0.232, p = 0.013) uniquely correlated with formation of distant metastases. Altered expression of PGs significantly correlated with the above disease outcomes when either considered alone or in association with well-established predictors of poor prognosis (i.e. T classification, previous occurrence of precancerous lesions and lymphnodal metastasis). Combined alteration of all three PGs was found to be a reliable predictor of shorter survival.

Conclusions: An unprecedented PG-based prognostic portrait is unveiled that incisively diversifies disease course in HNSCC patients beyond the currently known clinical and molecular biomarkers.
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http://dx.doi.org/10.1186/s12885-015-1336-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429505PMC
May 2015

Evidence of association of human papillomavirus with prognosis worsening in glioblastoma multiforme.

Neuro Oncol 2014 Jan 26;16(2):298-302. Epub 2013 Nov 26.

Corresponding author: Giuseppe Gasparre, PhD, Dipartimento di Scienze Mediche e Chirurgiche, UO Genetica Medica, Pad.11, Policlinico S.Orsola-Malpighi, via Massarenti 9, 40138, Bologna, Italy.

Background: Glioblastoma multiforme (GBM) is the most malignant brain tumor in adults, but its etiology still remains unknown. Recently, a role of viruses such as cytomegalovirus and JC virus in gliomagenesis has been suggested. Since human papillomavirus (HPV) is considered the most common oncogenic virus in humans, we evaluated its occurrence in GBM samples.

Material And Methods: Fifty-two formalin-fixed paraffin-embedded primary glioblastoma specimens were retrospectively analyzed. The presence of HPV genome on tumor DNA was assessed by MY/GP nested PCR. Confirmation of HPV detection was obtained by chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) with an antibody directed against the L1 capsidic protein. Finally, univariate and multivariate proportional-hazards models were used to compare the risk of death among HPV-positive and HPV-negative patients.

Results: Strikingly, viral DNA was detected after PCR in 12 cases (23%). HPV16 genome was present in 25% infected samples, whereas the remaining samples tested positive for HPV6. CISH confirmed positivity in all infected samples for which enough material was available. Moreover, IHC positivity suggested that production of viral proteins from HPV genome is an ongoing process in GBM cancer cells. Finally an association between HPV infection and a worse prognosis was found in patients upon age stratification with a univariate analysis (HR, 2.10; 95% CI, 1.00-4.44; log-rank P = .045).

Conclusions: HPV infection status may be considered an independent prognostic factor in GBM patients and suggests that prevention may be considered, should HPV be recognized as a causative agent in gliomagenesis.
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http://dx.doi.org/10.1093/neuonc/not140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895373PMC
January 2014

Galectin-3 expression in pituitary adenomas as a marker of aggressive behavior.

Hum Pathol 2013 Nov 2;44(11):2400-9. Epub 2013 Sep 2.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Section of Anatomic Pathology "M. Malpighi," Bellaria Hospital, Bologna 40139, Italy; Department Biomedical Sciences and Human Oncology, University of Turin, Turin 10126, Italy.

The purpose of this retrospective study was to investigate the role of galectin-3 (LGALS3) expression in predicting the recurrence and the progression potential of prolactin (PRL) and adrenocorticotropic hormone (ACTH)-producing pituitary adenomas and its correlation with the RUNX1 and RUNX2 transcription factors involved in the regulation mechanism of LGALS3 expression. Clinical, neuroradiologic, and follow-up data from 92 pituitary adenomas, including 59 PRL cell adenomas and 33 ACTH-functioning pituitary adenomas, were collected. The LGALS3 expression was analyzed by both immunohistochemistry and quantitative real time-polymerase chain reaction, whereas RUNX1 and RUNX2 were analyzed by quantitative real time-polymerase chain reaction only. The data obtained indicated that invasive growth with suprasellar extension, Ki-67 labeling index, and LGALS3 immunohistochemical and/or LGALS3 messenger RNA levels are the most important histologic features for assessing a high risk of progression or recurrence of PRL- and ACTH-functioning pituitary adenomas. Multivariate Cox regression analysis assessed LGALS3 immunohistochemical positivity in at least 30% of neoplastic cells and/or LGALS3 messenger RNA positivity (P < .001) as strong predictive factors of recurrence/tumor progression followed by a Ki-67 labeling index greater than 3% (P = .019) in the 81 cases in which follow-up data were available. In addition, a significant correlation between LGALS3 and RUNX1 expression levels (P = .0435) was found. This retrospective immunohistochemical and molecular study demonstrated that LGALS3 expression appeared to be a predictive factor of the aggressive behavior of PRL- and ACTH-functioning pituitary adenomas, and its expression was correlated with RUNX1 expression levels.
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http://dx.doi.org/10.1016/j.humpath.2013.05.020DOI Listing
November 2013

Oncocytic glioblastoma: a glioblastoma showing oncocytic changes and increased mitochondrial DNA copy number.

Hum Pathol 2013 Sep 9;44(9):1867-76. Epub 2013 May 9.

Department of Biomedical and NeuroMotor Sciences, University of Bologna, Section of Pathology, M. Malpighi, Bellaria Hospital, via Altura 3, 40139 Bologna, Italy.

Ten cases of glioblastomas showing oncocytic changes are described. The tumors showed mononuclear to multinuclear cells and abundant, granular, eosinophilic cytoplasm. The cytoplasm of these same cells was filled by strongly immunoreactive mitochondria. At ultrastructure, numerous mitochondria, some of which were large, were evidenced in the cytoplasm of neoplastic cells. Finally, 9 of 10 of these cases had a significantly high mitochondrial DNA content compared with control tissue (P < .01). It seems that, for these tumors, the designation of oncocytic glioblastoma is appropriate. To the best of our knowledge, oncocytic changes have not been previously reported in such neoplasms. Oncocytic glioblastomas have to be added to the long list of various tumors that can manifest "unexpected" oncocytic changes in different organs. Albeit failing to show statistical significance (log-rank test, P = .597; Wilcoxon test, P = .233), we observed a trend for longer median survival in oncocytic glioblastomas, when compared with "ordinary" glioblastomas (median survival of 16 versus 8.7 months). Thus, it seems that the definition of neoplasms showing oncocytic changes, currently based on classic morphological parameters (ie, histology, ultrastructure, and immunohistochemistry), can be expanded by including the quantitative assessment of mitochondrial DNA content.
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http://dx.doi.org/10.1016/j.humpath.2013.02.014DOI Listing
September 2013

Genetic relationship between multiple squamous cell carcinomas arising in the oral cavity.

Head Neck 2014 Jan 30;36(1):94-100. Epub 2013 Apr 30.

Section of Oral Science, Department of Biomedical and Neuro-Muscular Sciences, University of Bologna, Bologna, Italy.

Background: Histological and clinical criteria are generally used to differentiate second primary tumors (SPTs) from local recurrences. The purpose of the present study was to apply mitochondrial DNA (mtDNA) D-loop analysis to differentiate SPTs from local recurrences and to validate the clinical classification.

Methods: The study population consisted of 20 consecutive patients presenting multiple oral neoplastic lesions for a total of 25 paired lesions. The mtDNA D-loop analysis was performed by direct sequencing and phylogenetic clusterization.

Results: Agreement between mtDNA analysis and clinical classification was found in 19 cases. Discrepancies arose in 6 cases in which the clinical criteria based only on the spatial or temporal distance of the second lesion from the index tumor had led to a diagnosis of SPT (2 cases) or local recurrence (4 cases).

Conclusion: The present data highlight the value of mtDNA analysis in establishing the clonal relationship between the index tumor and the second neoplastic lesion.
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http://dx.doi.org/10.1002/hed.23259DOI Listing
January 2014

Podoplanin and E-cadherin expression in preoperative incisional biopsies of oral squamous cell carcinoma is related to lymph node metastases.

Int J Surg Pathol 2013 Apr 24;21(2):133-41. Epub 2013 Jan 24.

University of Bologna at Bellaria Hospital, Bologna, Italy.

Metastases to cervical lymph nodes (LNs) are an important independent adverse indicator in the prognosis of oral squamous cell carcinoma (OSCC). An accurate evaluation of molecular patterns favoring the metastatic process can be helpful in predicting cases of OSCC with elevated probability of early or late metastases and, moreover, in planning the proper therapeutic procedures before surgery. To this end, immunohistochemical expressions of both E-cadherin and podoplanin were evaluated on preoperative incisional biopsies of OSCC from 102 patients. The probability to have or develop metastases was very low when high E-cadherin expression was found in a preoperative sample or when a low podoplanin expression was found. Therefore, because of the strong association with LN metastases, high E-cadherin/low podoplanin immunohistochemical expression should also be assessed on preoperative incisional biopsies as a useful tool for evaluating the probability of early or late LN metastases of OSCCs.
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http://dx.doi.org/10.1177/1066896912471851DOI Listing
April 2013

Late skip lymph node metastasis of oral squamous cell carcinoma or metastasis of unknown second primary tumor? Answer by mitochondrial DNA analysis.

Oral Surg Oral Med Oral Pathol Oral Radiol 2014 Jan 20;117(1):e11-4. Epub 2012 Jul 20.

Maxillofacial Surgery Unit, Policlinico S. Orsola-Malpighi, "Alma Mater Studiorum," University of Bologna, Bologna, Italy.

Patients with head and neck squamous cell carcinoma (SCC) are at risk of developing additional tumors in the head and neck. The detection of a late lymph node metastasis poses a problem to the clinician: it could be a delayed regional metastasis or a new metastasis from a yet unknown second primary tumor. Differentiation between metastasis and recurrence of primary tumors versus second primary tumor may be difficult because all lesions have the histologic appearance of SCC. Differentiation between these possibilities, however, carries important differences in therapeutic and prognostic consequences. In the following case report we present an unusually late regional lymph node metastasis in a patient who was treated 4 years earlier for an SCC in the inferior alveolar ridge. The purpose of the present study was to apply mitochondrial DNA D-loop analysis to assess the clonal relationship between oral tumor and node metastasis.
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http://dx.doi.org/10.1016/j.oooo.2012.02.038DOI Listing
January 2014

A classification tree approach for pituitary adenomas.

Hum Pathol 2012 Oct 23;43(10):1627-37. Epub 2012 Mar 23.

Section of Anatomic Pathology, Department of Haematology and Oncology L e A. Seragnoli University of Bologna, Bellaria Hospital, 40139 Bologna, Italy.

It is difficult to evaluate the recurrence and progression potential of pituitary adenomas at presentation. The World Health Organization classification of endocrine tumors suggests that invasion of the surrounding structures, size at presentation, an elevated mitotic index, a Ki-67 labeling index higher than 3%, and extensive p53 expression are indicators of aggressive behavior. Nevertheless, Ki-67 and p53 labeling index evaluation is subject to interobserver variability, and their cutoff values are controversial. In the present study, the prognostic value of Ki-67 and p53 protein labeling indices and their correlation with clinical and radiologic parameters were evaluated using digital image analysis in a series of 166 pituitary adenomas in patients having undergone a follow-up of at least 6 years to evaluate the impact on the recurrence and progression potential of pituitary adenomas. The data were analyzed using the receiver operating characteristic curve and classification and regression tree analysis. The results showed that, in the unstratified data set, the commonly used threshold of the Ki-67 index of 3% has a high specificity (89.5%) but a low sensitivity (53.8%). Unsatisfactory performance results were obtained by performing receiver operating characteristic curve analysis on the p53 labeling index. On the contrary, the classification and regression tree analysis-derived tree demonstrated that each pituitary adenoma subtype has specific prognostic factors. Specifically, the Ki-67 labeling index is a useful prognostic factor in nonfunctioning, adrenocorticotropin, and prolactin adenomas, but with different thresholds. In conclusion, our study emphasizes that the term pituitary adenomas includes different types of tumors, each one having specific prognostic factors.
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http://dx.doi.org/10.1016/j.humpath.2011.12.003DOI Listing
October 2012

Reelin: a possible link between hippocampal sclerosis and cortical dyslamination in the setting of FCD type IIIa.

Neurol Sci 2012 Dec 28;33(6):1479-81. Epub 2011 Dec 28.

Section of Pathology, Department of Haematology and Oncology, University of Bologna, Bellaria Hospital, Via Altura 3, 40139, Bologna, Italy.

Reelin is a glycoprotein that acts as a stop signal for neuronal migration during brain ontogenesis. It plays an important role in the remodeling of the hippocampal formation and in stabilizing cortical architecture. We studied immunohistochemically 30 cases of focal cortical dysplasia (FCD) type IIIa to verify whether Reelin could represent the pathogenetic link between HS and cortical dyslamination in the setting of FCD type IIIa. Our results suggest that a subset of FCD type IIIa (namely abnormal cortical layering associated with MTS and GCD type 2) exists in which loss of Reelin appears to be the common pathogenetic basis. On the contrary in the other cases the presence of a common pathogenetic link remains to be demonstrated.
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http://dx.doi.org/10.1007/s10072-011-0895-7DOI Listing
December 2012

Nogo-A: a useful marker for the diagnosis of oligodendroglioma and for identifying 1p19q codeletion.

Hum Pathol 2012 Mar 10;43(3):374-80. Epub 2011 Aug 10.

Section of Pathology M. Malpighi, Department of Haematology and Oncological Sciences L. and A. Seragnoli, Bellaria Hospital, University of Bologna, 40139 Bologna, Italy.

The differential diagnosis between oligodendrogliomas and other gliomas remains a critical issue. The aim of this study is to verify the diagnostic value of Olig-2, Nogo-A, and synaptophysin and their role in identifying 1p19q codeletion. A total of 168 cases of brain tumors were studied: 24 oligodendrogliomas, 23 anaplastic oligodendrogliomas, 2 oligoastrocytomas, 2 anaplastic oligoastrocytomas, 30 glioblastoma multiforme, 2 diffuse astrocytomas, 4 anaplastic astrocytomas, 10 pilocytic astrocytomas, 9 ependymomas, 12 anaplastic ependymomas, 10 central neurocytomas, 10 meningiomas, 10 choroid plexus papillomas, 10 dysembryoplastic neuroepithelial tumors, and 10 metastases. All cases were immunostained with Olig-2, Nogo-A, and synaptophysin. In 79 cases, the status of 1p/19q had already been assessed by fluorescence in situ hybridization. Thus, in selected cases, fluorescence in situ hybridization was repeated in areas with numerous Nogo-A-positive neoplastic cells. Nogo-A was positive in 18 (75%) of 24 oligodendrogliomas, 8 (80%) of 10 dysembryoplastic neuroepithelial tumors, 6 (20%) of 30 glioblastoma multiforme, and 2 (20%) of 10 pilocytic astrocytomas. Olig-2 stained 22 (91.6%) of 24 oligodendrogliomas and all dysembryoplastic neuroepithelial tumors but also 24 (80%) of 30 glioblastoma multiforme and 8 (80%) of 10 pilocytic astrocytomas. Finally, synaptophysin stained 13 (54.1%) of 24 oligodendrogliomas, 3 (10%) of 30 glioblastoma multiforme, 1 (10%) of 10 pilocytic astrocytomas, and all neurocytomas. Among the 79 tested cases, original fluorescence in situ hybridization showed 1p/19q codeletion in 12 (52.2%) of 23 oligodendrogliomas, 8 (38%) of 21 anaplastic oligodendrogliomas, and 1 (4%) of 25 glioblastoma multiforme. However, after carrying out the Nogo-A-driven fluorescence in situ hybridization, 1p/19q codeletion was observed in 8 additional cases. Nogo-A is more useful and specific than Olig-2 in differentiating oligodendrogliomas from other gliomas. Furthermore, using a Nogo-A-driven fluorescence in situ hybridization analysis, it is possible to identify a larger number of 1p19q codeletions in gliomas.
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http://dx.doi.org/10.1016/j.humpath.2011.05.007DOI Listing
March 2012

IGFBP2 as an immunohistochemical marker for prostatic adenocarcinoma.

Appl Immunohistochem Mol Morphol 2011 Jul;19(4):318-28

Section of Anatomic Pathology, Department of Oncology and Hematology, University of Bologna, Bellaria Hospital, Bologna, Italy.

Aim: The aim of the study was to evaluate the immunohistochemical expression of insulin-like growth factor binding protein 2 (IGFBP2) in normal epithelium, high-grade prostatic intraepithelial neoplasia (HG-PIN), and prostatic adenocarcinoma (PAc), in patients hormonally untreated and in those having undergone complete androgen ablation.

Materials And Methods: IGFBP2 expression was evaluated in PAc, HG-PIN, and normal-appearing epithelium in 40 radical prostatectomies from hormonally untreated patients and 10 radical prostatectomies from patients under complete androgen ablation before surgery. The study also included the initial biopsies of such patients, and an additional 10 simple prostatectomies from patients with bladder outlet obstruction. Statistics included receiver-operator characteristic curves, the Wilcoxon test, and the Spearman test. Results were compared with α-methylacyl-CoA racemase.

Results: The principal findings were: (1) IGFBP2 was not expressed in normal ducts and acini of the transition and peripheral zones; (2) IGFBP2 was expressed in the cytoplasm of untreated PAc and, to a lesser extent, in HG-PIN; (3) it was also expressed in PAc and HG-PIN after complete androgen ablation, but to a lesser extent than in the untreated neoplasms; (4) α-methylacyl-CoA racemase was expressed both in PAc and HG-PIN, the level being similar in both lesions and lower in the specimens from the patients having undergone androgen ablation.

Conclusions: Results obtained show that IGFBP2 is expressed in invasive PAc, whereas its expression in HG-PIN is low. These findings can be helpful in the correct diagnosis of PAc both in biopsies and in surgical specimens, mainly in untreated patients.
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http://dx.doi.org/10.1097/PAI.0b013e3128052936DOI Listing
July 2011

Ki-67 from clinically and histologically "normal" distant mucosa as prognostic marker in early-stage (T1-T2N0) oral squamous cell carcinoma: a prospective study.

J Oral Maxillofac Surg 2011 Oct 3;69(10):2579-84. Epub 2011 Feb 3.

Department of Oral Science, University of Bologna, Bologna, Italy.

Purpose: The aggressive behavior and long-term prognosis of oral squamous cell carcinoma (OSCC) have recently been related to the mucosa surrounding the primary mass, consisting of genetically altered cells that might be responsible for cancer progression. Early-stage T1-T2N0 OSCCs have been associated with a good prognosis; however, a certain percentage of them can be complicated by locoregional metastases. The purpose of our study was to determine whether an abnormal proliferative status can be found in clinically and histologically "normal" mucosa situated in areas distant from the primary tumor. We also sought to determine whether this is associated with a poor prognosis in terms of local recurrence or lymph node metastasis.

Patients And Methods: The prospective study included 42 consecutive patients with T1N0M0 (n = 19) and T2N0M0 (n = 23) OSCC. Disease-free survival endpoints were defined as the duration between surgical resection and the diagnosis of recurrence, lymph node metastasis, or last follow-up visit. Proliferative status in distant areas (opposite cheek) was evaluated by Ki-67 expression.

Results: The mean Ki-67 value (17.6% ± 8.2%) in the distant mucosa was significantly greater (F = 13.87; P < .01) than that found in the controls (9.8 ± 3.1). "Abnormally high" Ki-67 values were detected in 13 patients with OSCC (30%). Four patients developed locoregional recurrence during follow-up. Kaplan-Meier analysis showed that Ki-67 in the distant mucosa was a significant independent prognostic factor for disease-free survival.

Conclusions: A certain percentage of patients surgically treated for early T1-T2 OSCC will have an abnormal proliferative status in areas very distant from the primary tumor that seems to be related to a poor prognosis.
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http://dx.doi.org/10.1016/j.joms.2010.10.041DOI Listing
October 2011

Cancerization of cutaneous flap reconstruction for oral squamous cell carcinoma: report of three cases studied with the mtDNA D-loop sequence analysis.

Histopathology 2011 Feb 24;58(3):361-7. Epub 2011 Jan 24.

Section of Anatomic Pathology, Department of Haematology and Oncology L. and A. Seragnoli, Bellaria Hospital, University of Bologna, Bologna, Italy.

Aims: Tissue defects, resulting from surgical resection of oral squamous cell carcinoma (OSCC), are reconstructed routinely with skin grafts. OSCC arising from the grafted skin has been described; however, it is still unclear whether primary and second tumours have a common clonal origin. The aim of this study was to evaluate the clonal relationship between the primary OSCC and secondary neoplastic changes appearing in the skin graft in three patients, by screening the mitochondrial DNA D-loop region (mtDNA).

Methods And Results: In all three cases, the neoplastic lesions arising in the skin graft showed a clonal relationship with the previous OSCC and, on the basis of the results obtained by mtDNA analysis, could be considered to be a recurrence of the primary OSCC rather than a second primary OSCC.

Conclusions: Starting from a field of genetically altered cells in the oral mucosa, the spread of the clonal cell population to the cutaneous flap might be stimulated by cytokines produced by the grafted skin. More studies are needed to evaluate the molecular relationship between primary and second OSCC to identify patients at higher risk of developing a second tumour in the skin graft.
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http://dx.doi.org/10.1111/j.1365-2559.2011.03754.xDOI Listing
February 2011

Oncocytic carcinoma of the breast: frequency, morphology and follow-up.

Hum Pathol 2011 Feb 26;42(2):166-75. Epub 2010 Nov 26.

Department of Haematology and Oncological Sciences L. and A. Seragnoli, Section of Anatomic Pathology at Bellaria Hospital, University of Bologna, 40139 Bologna, Italy.

Oncocytic breast carcinomas are tumors composed of no fewer than 70% of oncocytic cells (World Health Organization). The purpose of this study was to determine the frequency, morphologic, immunohistochemical, and clinical features of invasive oncocytic carcinoma in a large series. Twenty-eight cases of putative oncocytic breast carcinoma (selected cases group) and 76 consecutive cases of invasive breast carcinoma (consecutive cases group) were analyzed. Immunohistochemistry for mitochondria, gross cystic disease fluid protein 15, chromogranin, estrogen receptor, progesterone receptor, androgen receptor, HER2/Neu, cytokeratin 7, cytokeratin 14, epithelial membrane antigen, and differentiation cluster 68 was performed. Score for mitochondria was based on intensity and percentage of immunopositive cells. Classes were as follows: (1) oncocytic carcinoma: at least 70%, 3+; (2) mitochondrion-rich carcinoma: 50% to 70%, 3+, or more than 50%, 2+; and (3) all the other cases were referred to as invasive breast carcinoma. Ultrastructural examination was available for 6 cases of oncocytic carcinoma. Morphologic and immunohistochemical features of the 3 groups were compared using Fisher exact test (P < .05). For overall survival analysis, Kaplan-Maier curves were compared using log-rank and Wilcoxon tests (P < .05). Our results suggest that oncocytic breast carcinoma is a morphologic entity with distinctive histologic and ultrastructural features. Mitochondrion-rich carcinomas are histologically similar to oncocytic carcinomas and constitute 19.7% of all invasive carcinomas, indicating that cytoplasmic eosinophilia in breast cancer cells is often due to accumulation of mitochondria. Oncocytic carcinomas and mitochondrion-rich carcinomas are more often grade III tumors and show human epidermal growth factor receptor 2 overexpression. Clinical features and overall survival of oncocytic carcinomas are not distinctive because they are similar to those of the other cases when matched for grade and stage.
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http://dx.doi.org/10.1016/j.humpath.2010.07.014DOI Listing
February 2011

Immunohistochemical expression of p16(INK4A) protein as a helpful marker of a subset of potentially malignant oral epithelial lesions: study on a series with long-term follow-up.

Histopathology 2010 Oct;57(4):528-34

Department of Oral Sciences, University of Bologna Unit of Maxillo-Facial Surgery, Bellaria Hospital, Bologna, Italy.

Aim:   To examine a group of lesions that progressed to oral squamous cell carcinoma (OSCC) to determine whether p16(INK4A) expression is an early finding during malignant transformation, and whether immunohistochemical evaluation of p16(INK4A) is an appropriate prognostic marker.

Methods And Results:   Twenty cases of OSCC were investigated. All cases had had a biopsy on the same site as OSCC performed at least 1year before OSCC (range 1-11years; mean 3.15±3.1years). Twenty specimens from normal oral mucosa served as controls. p16(INK4A) expression was evaluated by immunohistochemical analysis and cases showing >5% of stained cells were defined as 'positive'. All 20 control cases were negative for p16(INK4A) . Oral lesions were p16(INK4A) -positive in nine cases and negative in 11. No significant relationship was found between p16(INK4A) positivity and the presence/absence of dysplasia. Among OSCC, nine tumours showed p16(INK4A) positivity and 11 showed negativity. A significant relationship (χ(2)=7.1; P<0.01) was found between the presence/absence of p16(INK4A) staining in OSCC and the presence/absence of p16(INK4A) staining in lesions preceding OSCC.

Conclusions:   p16(INK4A) immunohistochemistry has a potential role in detecting a subset of p16(INK4A) -positive lesions with malignant potential.
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http://dx.doi.org/10.1111/j.1365-2559.2010.03671.xDOI Listing
October 2010

Adenoid cystic carcinoma of the breast associated with invasive duct carcinoma: a case report.

Int J Surg Pathol 2011 Apr 19;19(2):230-4. Epub 2009 Feb 19.

Department of Hematology and Oncology, L. and A. Seràgnoli, Section of Anatomic Pathology, University of Bologna, Bellaria Hospital, Bologna, Italy.

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http://dx.doi.org/10.1177/1066896909332321DOI Listing
April 2011

Immunohistochemical expression of the human sodium/iodide symporter distinguishes malignant from benign gastric lesions.

Int J Surg Pathol 2009 Aug 4;17(4):327-34. Epub 2009 Jan 4.

Section of Anatomic and Histopathology, Department of Haematology and Oncology, "L. and A. Seragnoli" University of Bologna, Bellaria Hospital, Italy.

Aim: Sodium/iodide symporter (NIS) is a transmembrane protein that mediates the transport of I(-). The aim was to evaluate the immunohistochemical expression of the human homolog of NIS (hNIS) in a wide spectrum of gastric lesions.

Materials And Methods: Seventy-seven samples were stained immunohistochemically with a monoclonal antibody for hNIS, including 14 with normal gastric mucosa, 14 with chronic atrophic gastritis with foveolar hyperplasia, 15 with chronic atrophic gastritis with intestinal metaplasia, 6 with chronic atrophic gastritis with atypical regenerative hyperplasia, 8 with chronic atrophic gastritis with dysplasia, 15 with invasive adenocarcinoma, 3 with well-differentiated neuroendocrine tumor, and 2 with gastrointestinal stromal tumors (GISTs).

Results: hNIS stained the basolateral cytoplasmic portion of foveolae in normal mucosa, in 13 cases of chronic atrophic gastritis with foveolar hyperplasia, and in only 1 case of regenerative atypical hyperplasia. hNIS was consistently absent in intestinal metaplasia, in dysplastic glands, and in the cells constituting invasive carcinoma, well-differentiated neuroendocrine tumors, and GIST.

Conclusion: It seems that lack of hNIS can be useful in distinguishing foveolar hyperplasia from dysplastic glands.
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http://dx.doi.org/10.1177/1066896908329583DOI Listing
August 2009

Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20.

Virchows Arch 2008 Dec 25;453(6):599-609. Epub 2008 Oct 25.

Section of Pathology, Bellaria Hospital, University of Bologna, Bologna, Italy.

Thirty-nine glial tumours (28 glioblastomas (GB) and 11 low-grade gliomas) were investigated with DNA microarrays to reveal a possible specific gene expression profile. Unsupervised classification through hierarchical cluster analysis identified two groups of tumours, the first composed of low-grade gliomas and the second mainly composed of GB. Nine genes were identified as most informative: seven were over-expressed in low-grade gliomas and under-expressed in GB; on the contrary, two genes, insulin-like growth factor binding protein 2 (IGFBP-2) and cell division cycle 20 homologue (CDC20), were over-expressed in GB and under-expressed in low-grade tumours. This same genetic profile was confirmed by reverse transcriptase polymerase chain reaction. Immunohistochemistry for IGFBP-2 was positive in 88.8% of the cases of GB and in only one low-grade glioma, whilst CDC20 immunostained 74.1% of the cases of GB and none low-grade glioma. This was confirmed in an additional series of cases studied with immunohistochemistry only. In conclusion, over-expression of mRNA levels of IGFBP-2 and CDC20 is highly related to GB, IGFBP-2 and CDC-20 gene and protein expressions are strongly correlated, and IGFBP-2 and CDC20 immunopositivity can be useful for the identification of GB in small biopsies.
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http://dx.doi.org/10.1007/s00428-008-0685-7DOI Listing
December 2008

Epithelioid hemangioendothelioma of the spinal cord: Description of a case with cytogenetic analysis.

Int J Surg Pathol 2006 Oct;14(4):340-3

Section of Anatomic Pathology, Department of Oncological Sciences, University of Bologna, Bellaria Hospital, Bologna, Italy.

A case of epithelioid hemangioendothelioma of the cauda equina is reported. The patient presented with rapidly worsening low back pain. Magnetic resonance imaging revealed a sharply demarcated intradural lumbar lesion. A bluish-red lesion, attached to the filum terminale, was removed. The patient is alive without evidence of recurrence 18 months after surgery. The tumor was composed of variously sized vessels lined by epithelioid endothelial cells with clear cytoplasm and centrally located, moderately atypical nuclei. These cells were immunoreactive for CD31 and factor VIII antibodies. Cytogenetic analysis disclosed two clones: 44-45X, - Y [cp3]/46XY[11]. Epithelioid hemangioendothelioma may arise in several sites, the most common being soft tissues. It is a borderline tumor that may recur, may metastasize, and rarely causes death. The present case appears to be the first example of epithelioid hemangioendothelioma of the spinal cord.
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http://dx.doi.org/10.1177/1066896906292451DOI Listing
October 2006

Acquisition of i(8q) as an early event in malignant triton tumors.

Cancer Genet Cytogenet 2004 Oct;154(2):150-5

Department of Oncologic Science, Section of Anatomic Pathology, Bellaria Hospital, University of Bologna, Via Altura 3, 40139 Bologna, Italy.

Malignant triton tumors (MTT) are rare soft-tissue tumors characterized by a mixture of cells with nerve sheath and skeletal muscle differentiation. MTT is a histological variant of malignant peripheral nerve sheath tumors (MPNST). No characteristic cytogenetic anomaly has been detected in MPNST or MTT. In this paper, we report on the cytogenetic findings of an MTT from a 20-year old male with neurofibromatosis (NF1). The tumoral karyotype showed the modal number to be near-diploid and an abnormal karyotype with a Robertsonian translocation and 4 markers: 49,XY,der(14;15)(q10;q10),+4mar. Spectral karyotyping revealed the karyotype: 49,XY, der(14;15)(q10;q10),+i(8)(q10)x4. Fluorescence in situ hybridization analysis of the tissue confirmed the presence of the additional i(8)(q10) in all tumoral cells. The sequence analysis of p53 revealed a polymorphism in exon 9, codon 329. The two alleles, TTC and TCC, codify for phenylalanine and serine, respectively. Our results indicate that all neoplastic cells have the same cytogenetic pattern, suggesting that both cell lines, which show nerve sheath and skeletal muscle differentiation, are derived from a unique stem cell. The acquired Robertsonian chromosomal recombinants might represent an event in the tumorigenesis of MTT, and the present data suggest that genes located on 8q can be involved in the development of MTT.
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http://dx.doi.org/10.1016/j.cancergencyto.2004.02.007DOI Listing
October 2004

Cytogenetic analysis of myoepithelial cell carcinoma of salivary gland.

Virchows Arch 2004 Jan;444(1):82-6

Anatomia Patologica, Università di Bologna, Ospedale Bellaria, Via Altura 3, 40139 Bologna, Italy.

Myoepithelial cell carcinoma (MCC) of the salivary gland is a rare entity. Here, we describe the karyotype of MCC. The patient was a 53-year-old man, with a rapidly growing lesion of the palate. Despite complete surgical excision, radio- and chemotherapy, the lesion rapidly harboured local and distant metastases leading to the death of the patient, 4 months after the diagnosis. On histological and ultrastructural examination, the primary tumour and the related metastases were composed of oval and spindle cells, with features of myoepithelial cell differentiation reported in the literature. Cytogenetic analysis showed a composite karyotype in the primary tumour: 45-46,XY, +3[cp3]/ 44-45,XY, -17[cp4]/ 46,XY[5]. The lymph-node metastasis was near-triploid and showed a complex karyotype. Our cytogenetic data differ from those described in benign or slowly growing salivary gland tumours showing myoepithelial cell differentiation. It is suggested that highly aggressive tumours might follow a different pathway of malignant transformation.
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http://dx.doi.org/10.1007/s00428-003-0909-9DOI Listing
January 2004