Diagnostic and Prognostic Value of Isolated and Combined MCM3 and Glypican-3 Expression in Hepatocellular Carcinoma: A Novel Immunosubtyping Prognostic Model.

Despite diagnostic and therapeutic advances, hepatocellular carcinoma (HCC) remains a leading cause of morbidity/mortality worldwide. This retrospective study investigates the isolated and combined mini-chromosome maintenance complex component 3 (MCM3) and glypican-3 (GPC3) immunohistochemical (IHC) expression in HCC. A novel HCC immunosubtyping model based on combined MCM3/GPC3 expression is introduced and tested in comparison with prognostic variables and survival outcomes. Seventy-six HCC patients who underwent hepatectomy were enrolled. After the collection of clinicopathological, laboratory, and 3-year-survival data, IHC was applied to HCC tissue microarray-prepared sections using anti-MCM3 and GPC3. IHC scoring divided HCCs as: MCM3-high and MCM3-low expression, GPC3-positive and GPC3-negative expression, and combined scoring model immunosubtypes: MCM3-high/GPC3-positive; MCM3-low/GPC3-positive; MCM3-high/GPC3-negative, and MCM3-low/GPC3-negative. Statistical and Kaplan-Meier survival analyses were performed using SPSS version 23. MCM3 was expressed in 84.2% of HCCs. MCM3-high HCCs (60.5%) were significantly associated with lack of tumor capsulation, portal vein thrombosis, high grades, advanced stages, and Child-Pugh Scores B and C (all P≤0.05), and had a tendency for multiplicity, metastasis, solid growth pattern, shorter overall survival (OS) and disease-free survival (DFS). GPC3-positve HCCs (56.6%) were significantly associated with multiplicity and higher alfa-fetoprotein (all P≤0.05) with a tendency for shorter OS and DFS. Among all isolated and combined-expression immunosubtypes, MCM3-high/GPC3-positive HCCs had the worst prognosis and the shortest OS and DFS whereas MCM3-low/GPC3-negative immunosubtype showed the best prognosis and had the longest OS and DFS. MCM3 is defined as diagnostic, prognostic marker, and potential therapeutic target in HCC. The novel MCM3/GPC3 immunosubtyping model provides prognostic indications and stratification criteria for patients with HCC.

Accuracy and Upgrading of CNB and BI-RADS Diagnoses Compared to Excision: A Clinicopathological-Radiological Correlation of Papillary Breast Lesions and Neoplasms.

BACKGROUND: Papillary breast lesions and neoplasms (PBLs/Ns) are diagnostically challenging lesions in both core needle biopsy (CNB) and radiology. AIM: To determine the accuracy and upgrade rate of CNB and BI-RADS diagnosis of PBLs/Ns compared to final excision diagnosis and the factors linked to upgrade. METHODS: The favored CNB diagnosis and BI-RADS category for 82 PBLs/Ns were assessed based on histopathology, myoepithelial marker immunohistochemistry, mammographic/ultrasonographic findings. The radiological findings were compared to the pathological diagnoses. The accuracies of CNB and BI-RADS were compared to the excision diagnosis of the corresponding PBLs/Ns. The upgrade rates to malignancy were evaluated for both CNB and BI-RADS. RESULTS: The presence of solid, irregular masses in breasts with composition A/B with calcification in radiology was significantly associated with the diagnosis of suspicious/malignant CNB, and malignant excision specimens (p<0.05). CNB was more accurate (90%), sensitive and specific with high positive and negative predictive values than BI-RADS. Combined CNB/BI-RADS accuracy was 90.2%. Overall upgrade rate came up to 9.8%. Upgrade rates to carcinoma were 7.3% for CNB and 8.5% for BI-RADS. Factors linked to upgrade were the age, lesion-size, BI-RADS category 4A and C, and histopathological/radiological discordance. All the upgraded PBLs/Ns were diagnosed as benign lesions in CNB with present/focally present myoepithelial diagnosis reflecting a sampling error. CONCLUSION: Up to 9.8% of PBLs/Ns diagnosed on CNB and BI-RADS undergo upgrading upon final excision, despite the high diagnostic accuracy. These evidences should be considered for final decision on whether to excise the lesion or not.

Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status.

OBJECTIVE: Programmed death-ligand 1 (PD-L1) and human epidermal growth factor receptor 2 (HER2) are currently considered as prognostic markers and therapeutic targets in many human cancers. This study aims to evaluate immunohistochemical (IHC) expression of PD-L1 in gastric cancer (GC) and explore its prognostic role in terms of association with HER2 expression, different clinico-pathological variables, in particular density and cluster designation (CD)8 positivity in tumor infiltrating lymphocytes (TILs) and with patients' disease-free and overall survival (DFS, OS). METHODS: This retrospective cohort study included 111 diagnosed primary GC patients who underwent surgical resection at the Gastrointestinal Surgery Center (GISC), Faculty of Medicine, Mansoura University, Egypt. After demographic, clinicopathological and survival data collection, histopathological evaluation was done for GC typing, staging and assessment of the histopathological prognostic parameters. IHC was performed for PD-L1, HER2 and CD8. PDL-1 was scored using the Combined Positive Score (CPS). RESULTS: PD-L1 was expressed in 43.2% of GCs at a CPS cut-off value ≥ 1. PDL-1 positivity was significantly associated with high TILs and CD8+ TILs (p=0.008, 0.016 respectively), indicating its contribution to tumor microenvironment along with the TILs. Multivariate analysis spotted PD-L1 positivity as an independent prognostic predictor for shorter OS in GC (p=0.013), with a tendency toward shorter DFS. Only 9.9% GCs were HER2 positive (score +3) with no significant association with PD-L1. CONCLUSION: PDL-1 is a promising prognostic and therapeutic target in GC that may direct the selection of patients for immunotherapy and checkpoint-blockade (pembrolizumab) therapy.

Isolated Myeloperoxidase Immunohistochemical Expression in Bone Marrow Biopsy Depicts Clinical Outcomes in Adults with Typical B-Acute Lymphoblastic Leukemia.

INTRODUCTION: Recently, isolated myeloperoxidase expression (isoMPO) has been documented in B-acute lymphoblastic leukemia (B-ALL) and several contradictory studies addressed its clinical significance in pediatric patients. AIM: In this study, isoMPO was evaluated in bone marrow biopsies (BMB) from adults with B-ALL using immunohistochemistry (IHC) in relation to a number of risk-stratification factors and patients' outcomes. METHODS: Sixty B-ALL adult patients were selected upon electronic database search. Demographic, clinical, laboratory, therapy and survival data were reviewed and tabulated. Flowcytometry (FCM), histopathology and IHC available material were reviewed to confirm the diagnostic criteria according to our standard laboratory protocols. IHC was performed on BMB using antiMPO. Cases were divided into MPO+ve and MPO-ve based on a 3% blast cell staining threshold. RESULTS: Using IHC, 26.7% of B-ALLs were MPO+ve, in most of which ≥10% of blasts were stained. Among standard risk-stratification factors, isoMPO was associated with a mean WBC count above 30x109/L. MPO+ patients achieved therapeutic complete remission at lower rates and were more prone to progressive/refractory disease and relapse. There was a concordant expression of MPO in FCM and IHC. All of the aforementioned parameters reached the level of significance when compared to the MOP-ve group. Kaplan-Meier curves revealed a significantly lower survival probability for the MPO+ group than the MOP-ve one (p= 0.0066; Log-rank test) and also when separating MPO+ and -ve patients by gender (p= 0.0033; Log-rank test). CONCLUSION: isoMPO occur in a considerable percentage of B-ALL in adults contributing to misdiagnosis. It depicts poor outcomes and might be introduced as a B-ALL risk-stratification factor.
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High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer.

BACKGROUND: Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC). AIM: This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient's outcome. METHODS: Patient's socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis. RESULTS: FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor's anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor's anatomical extent and tumor's size (p ≤ 0.001, = 0.046 and = 0.023 respectively). CONCLUSION: FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

Neutrophil extracellular traps-associated protein peptidyl arginine deaminase 4 immunohistochemical expression in ulcerative colitis and its association with the prognostic predictors.

Neutrophil extracellular traps (NETs) are incriminated in several immune and inflammatory diseases including ulcerative colitis (UC). Analysis of colonic tissues for NETs-related markers in UC carries prognostic and therapeutic implications. This work aims to evaluate the immunohistochemical (IHC) expression of NETs-associated-protein arginine deaminase 4 (PAD4) in colonic biopsies from UC patients in comparison to normal colon (NC). Association between PAD4 expression level and histopathologic grade, patient's therapeutic response and other clinicopathological prognostic predictors in UC are determined. This cohort study included biopsies from 42 UC patients and 11 NC controls. Clinicopathological data including patient's age at diagnosis, gender, presenting symptoms, anatomical disease extent, extra-intestinal manifestations, type and response to therapy and surgical interventions were recorded and tabulated. Histopathological grading of disease activity and associated epithelial changes were assessed. PAD4 immunostaining was conducted using Horseradish Peroxidase technique and scored semiquantitatively considering intensity and percentage of nuclear staining of lamina propria inflammatory cells. Appropriate statistical tests were applied. Anti-PAD4 was localized mainly in the nuclei of lamina propria infiltrating neutrophils. It was expressed more significantly in UC (95.2 %) compared to NC (p 0.001). Increased PAD4 expression level was significantly associated with increasing histopathologic grade, anatomical disease extent, lacking response to therapy and subjection to radical surgery (p:0.001, = 0.038, 0.046, 0.046 respectively). Age, gender, presenting symptoms, extra-intestinal manifestations and epithelial changes showed insignificant associations. This study characterizes a subset of UC patients with high histopathological grade of activity, pancolonic involvement, strong/moderate PAD4 expression levels and who are unresponsive to routine medical therapeutic regimens rendering them candidates for radical surgery. In conjunction with histopathological grading, IHC evaluation of PAD4 in UC is recommended to guide patient's selection for targeted therapy using the novel-discovered selective PAD4 inhibitors.

WT1 Clone 6F-H2 Cytoplasmic Expression Differentiates Astrocytic Tumors from Astrogliosis and Associates with Tumor Grade, Histopathology, IDH1 Status, Apoptotic and Proliferative Indices: A Tissue Microarray Study.

OBJECTIVES: This tissue microarray (TMA) immunohistochemical (IHC) study elucidates the role of Wilms' tumor 1 protein (WT1) in diagnosis and prognostication of astrocytic tumors. METHODS: IHC was applied to 75 astrocytic lesions (18 astrogliosis and 57 astrocytic tumors) using antibodies directed against WT1 clone 6F-H2, isocitrate dehydrogenase 1(IDH1), Bcl2 and Ki67. WT1 IHC staining was evaluated and scored blindly by 2 pathologists. Bcl2 and Ki67 scores and labelling indices were assessed and IDH1 status determined. Statistical analysis was performed using the appropriate methodology. RESULTS: WT1 cytoplasmic expression was detected in 89.5% of astrocytic tumors but not in astrogliosis. Positive WT1 differentiated astrocytic tumors (92.6% accuracy) and grade II diffuse astrocytomas (93.5% accuracy) from astrogliosis with high sensitivity, specificity and positive predictive values (p<0.001). Increased WT1 score significantly associated higher Bcl2 and Ki67 labelling indices, increasing WHO tumor grade and tumor's histopathologic type (p<0.05) showing staining pattern variability by tumor entity and cell type. Glioblastomas, gliosarcomas and subependymal giant cell astrocytomas were the most frequently WT1 expressing tumors with frequent +3 WT1 score. About 21.4% of pilocytic astrocytomas had +3WT1 score in association with increased Bcl2 and Ki67 indices. Low WT1 scores in grade II and III diffuse astrocytomas were linked to the high frequency of IDH1 positivity, and were associated with low Bcl2 and Ki67 labelling indices. In glioblastomas, WT1 significantly associated poor prognostic variables: older age, negative-IDH1 status, high Bcl2 and Ki67 labelling indices (p=0.04, <0.001, =0.001 and.

Ki67 and CD31 Differential Expression in Cutaneous T-Cell Lymphoma and Its Mimickers: Association with Clinicopathological Criteria and Disease Advancement.

BACKGROUND: Cell proliferation and angiogenesis are important in progression of cancerous processes. Differentiating cutaneous T-cell lymphoma (CTCL) from its mimicking dermatoses and prognosticating it are challenging. AIM: This study assesses cell proliferation and angiogenesis in different CTCL subtypes using immunohistochemistry (IHC) for Ki67 and CD31 to testify their usability in differentiating CTCL from mimicking dermatoses and discriminating CTCL subtypes from each other with correlation to clinicopathological parameters and disease advancement. PATIENTS AND METHODS: IHC for Ki67 and CD31 were applied to skin biopsies from 81 patients divided into CTCL (n=59) and dermatoses (n=22) groups. Hot-spot analysis was used to score Ki67 and CD31 microvascular density (MVD) semiquantitatively. Statistical analysis was performed to compare Ki67 index and MVD between CTCL and dermatoses. CTCL subgroups were compared to each other. Ki67 index and CD31 were compared to age, gender, skin and nodal involvement, blood tumor burden and TNMB stage. RESULTS AND CONCLUSION: There were significant differences in proliferation index and MVD between dermatoses and CTCL, and between dermatoses and all CTCL subtypes with exception of Ki67 in early mycosis fungoides (MF) and CD31 in patch lesions. Increased cell proliferation and MVD were significantly associated with older age, T3 and 4 skin involvement, significant nodes (N1-3), positive blood tumor burden (B1,2) in CTCL and TNMB stage of MF. Both markers differentiated significantly late from early MF, classic MF from its variants and non-MF CTCL from total MF, but not from late MF. In conclusion, Ki67 and CD31 expression in skin biopsies using IHC reproduces the role of proliferation and angiogenesis in the differential diagnosis and prognostication of CTCL being expressed at higher levels in aggressive than indolent CTCL. Therapeutic targeting of cell proliferation and angiogenesis may improve patient's outcome in CTCL. Usability of these markers into patient's stratification should be considered in further studies.

Clinicopathological Criteria Defining Mucinous Appendiceal Tumors from 2476 Appendectomies: a Single-Center Retrospective Study.

OBJECTIVES: Mucinous appendiceal tumors (MATs) constitute 0.2-0.3% of appendectomies. This retrospective chart review study determines the incidence of MATs among appendectomies at King Abdul-Aziz Specialist Hospital, Taif City, Saudi Arabia, from January 2009 to December 2014. The clinicopathological features, histopathological criteria, management, outcomes of patients, and the impact of histopathological classification on the follow-up period and recurrence are evaluated. METHODS: Demographic and clinicopathological data were collected from medical records. Microscopic slides from 2476 appendectomies were re-examined to diagnose and classify MATs into low-grade mucinous neoplasms (LAMNs) and mucinous adenocarcinomas (MACAs). CK20, CK7, and cdx2 immunohistochemistry was applied for evaluating pseudomyxoma peritonei. Data were expressed as numbers, percentages, and mean ± standard deviation. RESULTS: Nine MATs were diagnosed with an incidence of 0.36% of appendectomies, a male:female ratio of 1.25:1 and a mean age of 57.2 years. Acute appendicitis was the commonest clinical presentation. About 66.7% were LAMNs and 33.3% MACAs. Beside appendectomy, MACAs were managed with right hemicolectomy and chemotherapy. The median follow-up was 34 months with recurrence and liver metastases in two MACAs. No recurrences for LAMNs. CONCLUSIONS: MATs constitute 0.36% of all appendectomies. Classifying MATs into LAMNs and MACAs is more applicable for both clinical and pathology practices as compared to the three- or four-tiered classification schemes.

Cytomorphologic patterns of Pap and PAS-stained oral exfoliative cytology smears in adult Saudi diabetic patients as compared to healthy controls.

INTRODUCTION: Diabetes mellitus (DM) is one of the most common metabolic disorders worldwide and 425 million people were estimated to have diabetes by 2017. Oral manifestations reflect the metabolic control of diabetes. Exfoliative cytology using Papanicolaou (Pap) and periodic acid Schiff (PAS) stains is a practical technique to evaluate oral epithelial cytomorphologic changes in diabetes. AIM: This study analyzes the cytomorphologic changes and the glycogen content in exfoliated oral epithelial cells among diabetic patients as compared to healthy controls using Pap and PAS stains to verify the utility of exfoliative cytology as adjunct to diagnosis, follow up or screening of diabetes. SUBJECTS AND METHODS: Eighty-nine participants; 38 adult diabetic patients (case group) and 51 age-matching nondiabetics (control group) were enrolled in the study after fulfilling appropriate inclusion and exclusion criteria. Sampling and staining procedures were performed using routine protocols. Slides were observed by two pathologists and categorized as inflammatory, dyskaryotic and negative. Glycogen content was expressed as PAS negative or +, ++, and +++ positive. RESULTS: The difference between the diabetics and the controls was statistically significant regarding inflammatory, dyskaryotic/nuclear changes and glycogen content and staining intensity. Other observed finding in diabetic patient smears included binucleation, polychromic, and/or vacuolated cytoplasm. CONCLUSIONS: Cytomorphologic changes of oral epithelial cells reflect the complex pathological mechanisms by which DM affects cellular metabolism and function. Cytomorphologic patterns of Pap and PAS-stained oral exfoliative cytology smears can be helpful for diagnosis, follow up as well as for screening for diabetes in high prevalence communities.

Can vitamin C affect the KBrO3 induced oxidative stress on left ventricular myocardium of adult male albino rats? A histological and immunohistochemical study.

Potassium bromate (KBrO3) cardiotoxicity is not widely recognized, in spite of its well known oxidative cell and tissue damage. The wide exposure to KBrO3 in food and water necessitates finding of a simple and available antidote for its hazards like vitamin C. There are growing evidences that the regulation of redox reactions in cells is intimately tied to the levels of antioxidants. As the heart is highly vulnerable for oxidative damage, left ventricle muscle was the spotlight of our study. For this purpose 20 adult male albino rats were categorized into four groups (five rats each). Group 1 served as control; group 2 received 30 mg/kg/day vitamin C for 4 weeks. Group 3 was injected intraperitoneally with KBrO3 20 mg/kg/dose twice weekly for 4 weeks, and group 4 received both vitamin C and KBrO3 in the same scheme. Heart specimens were processed for various histological examinations. Sections from KBrO3 treated animals showed focal disruption of cardiac myocytes, deeply stained nuclei and dilated congested blood vessels. Ultrastructurally, irregular indented nuclei, focal lysis of the myofibrils and swelling of mitochondria were also observed. In contrast, minimal changes were observed in rats treated concomitantly with both vitamin C and KBrO3. Caspase 3 immunohistochemical reaction was nonsignificantly increased in group 3 cardiomyocytes. Semiquantitative morphological mitochondrial scoring and statistical analyses revealed significant changes between the studied groups. Finally, KBrO3 induced structural changes in rat cardiac muscle could be ameliorated by concomitant treatment with vitamin C.

Limited reliability of five non-invasive biomarkers in predicting hepatic fibrosis in chronic HCV mono-infected patients opposed to METAVIR scoring.

BACKGROUND: Liver biopsy is gold standard for fibrosis assessment in hepatitis C virus (HCV) infection but its limitations led to the identification of non-invasive biomarkers. This study assesses the reliability of five biomarkers in estimating the stage of liver fibrosis/cirrhosis in chronic HCV patients versus METAVIR scoring. METHODS: One hundred HCV monoinfected patients who underwent liver biopsy and blood sampling were included. Liver fibrosis was staged (F0-4) and required laboratory tests were performed. AAR, API, APRI, FIB-4 and Pohl score were calculated and their receiver operating curves (ROCs), sensitivities, specificities, predictive values and accuracies were evaluated. RESULTS: There were 27, 44, and 29 patients at F0-F1, F2-F3, and F4 groups. Significant statistical differences were found regarding AST, vireamia, platelet count, prothrombin time and all biomarkers. From ROCs only Pohl score predicted significant fibrosis and cirrhosis but with low accuracy. AAR, API and APRI showed moderate performance at low cut-offs, but had limited predictive values or accuracies at higher cut-offs. FIB-4 was the least accurate test. The diagnostic reliability of these biomarkers was limited to patients with suspected insignificant fibrosis. CONCLUSIONS: This study verified the limited reliability for AAR, API, APRI, FIB-4 and Pohl score in estimating the stage of hepatic fibrosis in HCV infected patients opposed to METAVIR scoring.

Immunohistochemistry-based subtyping of breast carcinoma in Egyptian women: a clinicopathologic study on 125 patients.

Breast carcinoma is a heterogeneous disease affected by patients' ethnicity. Gene expression analysis identified several molecular subtypes, and similar subtyping has now been found to be feasible using immunohistochemistry. This study estimated the distribution of intrinsic breast cancer subtypes using estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (Her2/neu), and cytokeratin 5/6 immunostaining in a cohort of 125 Egyptian women diagnosed as having invasive breast carcinoma. Associations with clinicopathologic variables and the prognostic markers Bcl-2 and Cyclin D1 were investigated and statistically analyzed. Population difference in breast cancer subtypes was detected, suggesting etiologic and genetic heterogeneity among demographic groups. As reported worldwide, most tumors were luminal A (39.2%), but basal-like and unclassified subtypes had higher proportions among our cohort (16.8% and 16%, respectively), particularly in premenopausal patients (P = .0001), in contrast to postmenopausal African Americans, premenopausal European Americans, and other populations. Her2-overexpressing subtype was the least common subtype (13.65%) among our patients, although it is more common in Asians. Basal-like and unclassified carcinomas were more frequently grade 3 neoplasms (P = .035). Lobular histology was distributed among luminal A, B and unclassified subtypes (P = .006). The highest frequency of nodal positivity was associated with Her2 overexpressing carcinomas (94.1%, P = .0001). Luminal and unclassified carcinomas more likely expressed Bcl-2 (P = .011) and Cyclin D1 (P = .0001), whereas basal and Her2 subtypes had the lowest expression levels. Immunohistochemistry-based subtyping can be helpful in separating breast carcinoma into subtypes that vary in distribution among different populations. These subtypes have distinct clinicopathologic features and diverse prognostication, which may imply different therapeutic options for each subtype.

Immunohistochemical expression and prognostic relevance of Bmi-1, a stem cell factor, in epithelial ovarian cancer.

Ovarian cancer is the fourth most common cause of cancer-related death in women. Bmi-1 is a stem cell factor implicated in many human malignancies with poor outcome. Few published reports on the expression of Bmi-1 in epithelial ovarian cancer were either experimental or performed on cell lines. This study evaluates the immunohistochemical expression of Bmi-1 protein in epithelial ovarian cancer tissue specimens and its relevance to the clinicopathologic prognostic variables and patient survival. Forty cases of epithelial ovarian cancer were selected according to the availability of paraffin-embedded tissue and the clinicopathologic and survival data. Immunohistochemistry was performed for anti-Bmi-1 antibody. Low and high Bmi-1 expression groups were compared with age, tumor stage, laterality, grade, histology, and patient survival. Bmi-1 expression was detected in 72.5% of cases, of which 42.5% had high expression. High Bmi-1 expression strongly associated with advanced International Federation of Gynecology and Obstetrics stages (P = .007), bilaterality (P = .01), and higher Gynecologic Oncology Group grades (P = .031) and carcinomas of serous histology (P = .027). It had no association with patient age. Bmi-1 expression displayed a significant inverse association with patient overall and mean survival (P = .006, P < .001). These observations suggested correlation between increased Bmi-1 expression and clinical progression in ovarian epithelial cancer.

Analysis of metaplastic breast carcinoma: FNAC; histopathology and immunohistochemistry are complementary for diagnosis.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare malignancy comprised of ductal, squamous and/or mesenchymal elements with problematic diagnosis. OBJECTIVE: This study analyses MBC identifying its cytologic and histologic features and emphasizing the combined role of FNAC, histopathology and immunohistochemistry (IHC) in its diagnosis. MATERIALS AND METHODS: Cytology and histopathology files search yielded 21 cases identified as MBC from January 2005 to December 2010. FNAC and the histopathology slides were re-examined for the presence and frequency of various elements. Cytological and histopathological diagnoses were made and the cases subtyped according to WHO classification. Cytokeratin and vimenten IHC were used to confirm diagnosis when required. RESULTS: On FNAC, 52.4% were diagnosed as malignant, 9.5% as suspicious for malignancy and 38.1% as benign lesions. Most frequent cytologic findings were squamous and spindle cell elements (52.4% each). Histopathology revealed 76.2% pure epithelial tumors and 23.8% mixed epithelial-mesenchymal tumors. Squamous cell carcinoma was the most frequent histological subtype (33.3%). Carcinosarcomas were dimorphic on IHC& spindle cell carcinomas were positive for both cytokeratin and vimentin. CONCLUSION: Presence of dual components, squamous, spindle elements, mesenchymal fragments and necrosis in moderate to high cellularity breast FNAC provides clues for the diagnosis of MBC. FNAC; histopathology and IHC complement for diagnosis.

Diagnostic spectrum of ovarian masses in women with breast cancer; magnetic resonance imaging: histopathology correlation.

This study addresses the clinical problem of the patient with breast cancer that has been operated on for an ovarian mass. It specifies the spectrum of histopathologic diagnoses and the differentiating magnetic resonance imaging (MRI) features of ovarian masses with correlations between clinical features, histopathologic, and MRI findings. Sensitivity and specificity of MRI vs histopathology in diagnosing malignancy are estimated. The study included 53 women with breast cancer who underwent surgery for an ovarian mass. Complete medical records, US and MRI images for the ovarian mass, and histopathology slides of both breast and ovarian resection specimens were reviewed and analyzed retrospectively. Thirty-six (67.9 %) patients had benign masses, and 17 (32.1%) had malignant masses, of which 8 (15.1%) were primary ovarian malignancies and 9 (17%) were metastatic from breast carcinomas. There was a significant association between benign and primary malignant ovarian masses and stage II breast cancer (P = .00). There was a significant association between metastatic ovarian masses and stage III to IV breast disease (P = .00) and negative estrogen receptor status (P = .05). Magnetic resonance imaging had a specificity of 91.7% and a sensitivity of 94.1% in diagnosing malignant ovarian masses. In conclusion, the spectrum of ovarian masses diagnosed in patients with breast cancer is broad, including benign lesions, primary ovarian malignancies, and breast metastases. Knowledge of the imaging features may allow a specific diagnosis aiding in surgical planning. Despite the high specificity and sensitivity of MRI to differentiate benign from malignant lesions, the unique ability to differentiate between primary and metastatic malignancies is conserved to histopathology.

Different prognostic factors correlate with Bcl-2 expression among triple negative and non-triple negative breast cancers.

BACKGROUND: Prognostication of breast cancer using clinico-pathologic variables, although useful, remains imperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling. Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focused on Bcl-2 protein expression in triple-negative (TNBC) and non- triple-negative breast cancer (non-TNBC) with correlation to clinico-pathologic variables. MATERIALS AND METHODS: We analyzed Bcl-2 expression in 77 women with primary breast carcinoma divided into two groups; triple-negative and non- triple-negative according to expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2 expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. RESULTS: Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non- triple-negative cancers. In TNBC, expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantly correlated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourable prognostic factors in breast cancer, but no significant statistical correlations were found. CONCLUSIONS: Frequency of Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlate with Bcl-2 in the two cases.