Assessment of HER2 Status Using Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) Techniques in Mucinous Epithelial Ovarian Cancer: A Comprehensive Comparison between ToGA Biopsy Method and ToGA Surgical Specimen Method.

We aimed to compare the assay performance characteristics of HER2 status in mucinous epithelial ovarian cancer (EOC) by ToGA (Trastuzumab for Gastric Cancer) biopsy versus ToGA surgical specimen methods. Forty-nine tissue microarray (TMA) samples of mucinous EOC from Asian women were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests using ToGA trial HER2 scoring methods. The overall concordance between IHC and FISH by the ToGA surgical specimen method is 97.56% and by the ToGA biopsy specimen method is 97.14%. The agreements of HER2 IHC results under both biopsy and surgical specimen methods were nearly perfect (weighted kappa = 0.845). Additionally, the percentage of Her2 FISH amplification showed increasing trend with increasing HER2 IHC ordinals (negative, equivocal, positive) by both TOGA biopsy (P<0.001) and surgical specimen method (P<0.001). After excluding equivocal cases, the sensitivity (100%), PPV (88.89%) and NPV (100%) of HER2 IHC were unchanged under either surgical specimen method or biopsy method. However, the specificity (96.97%) and accuracy (97.56%) of HER2 IHC was slightly higher under the surgical specimen method than those (specificity 96.30%, accuracy 97.14%) under the biopsy method. Of the total 49 cases, the number (n = 14) of HER2 IHC equivocal results under the ToGA biopsy method was 1.75-fold higher than those (n = 8) under the ToGA surgical specimen method (28.57% vs. 16.32%). Therefore, compared to ToGA surgery specimen method, the ToGA biopsy method caused more equivocal IHC cases to be referred to FISH testing and did not increase the detection rates of Her2 FISH amplification.

Extranodal natural killer/T-cell lymphoma, nasal type in Taiwan: a relatively higher frequency of T-cell lineage and poor survival for extranasal tumors.

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a predominantly extranodal lymphoma associated with Epstein-Barr virus occurring most frequently in the upper aerodigestive tract. There are limited reports on cellular origin and prognostic factors. We retrospectively investigated 73 cases with a median age of 54 years and a male-female ratio of 2.0:1. The upper aerodigestive tract (nasal group) was the most common site of involvement (51 cases; 70%). The other organs (n = 22; extranasal group) included the skin (12 cases; 16%) and gastrointestinal tract (5; 7%). Of the 70 cases with complete staging, 71% had stage I/II disease. All cases were positive for Epstein-Barr virus by in situ hybridization. Using immunohistochemistry and clonality assay for T-cell receptor gene rearrangement, these tumors were classified into NK (n = 39; 53%), T (n = 13; 18%), and indeterminate lineage (n = 21; 29%). The only clinicopathological difference among these 3 groups was rare CD5 expression in the NK-cell group. Nasal tumors were more frequently of NK-cell origin, and extranasal tumors were equally of either T- or NK-cell origin. The 5-year overall survival rate was 35.6%. The overall survival time was shorter in the extranasal group, although there was no statistical difference in age, sex, and histologic or immunophenotypic features between the 2 groups. Excluding the cases with indeterminate lineage, 75% of cases were of NK lineage; and 25%, T lineage. Extranasal tumors were more aggressive than their nasal counterparts. A prospective national study is warranted for a better understanding of the clinicopathological and genetic features of this uncommon tumor and the prognostic factors.

Assessing the HER2 status in mucinous epithelial ovarian cancer on the basis of the 2013 ASCO/CAP guideline update.

Her2 gene amplification and protein overexpression are important factors in predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in breast, gastric, or gastro-esophageal junction cancer patients. The purpose of this study was to evaluate the HER2 status in the mucinous epithelial ovarian cancer (EOC). Adopting the 2013 American Society for Clinical Oncology and the College of American Pathologists guideline update for HER2 testing, 49 tissue microarray samples of mucinous EOC were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests. The prevalence of HER2 positivity in Asian mucinous EOC was 9 of 49 Asian women (18.37%). The overall concordance was 100% between IHC and FISH results. Her2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal, and positive IHC result categories (P<0.001), as did the Her2 gene copies after chromosome-17 correction (P<0.001). Of the Taiwanese cohort (n=21), HER2 heterogeneity was 4.76% (1/21) in all but 14.26% (1/7) in HER2-positive cancer. In conclusion, we demonstrated that the prevalence of HER2 positivity in both Asian and white women was comparable; complete HER2 concordance existed between IHC and FISH tests for the Her2 gene copies per tumor cell either before or after correction of chromosome-17, and this can be applied as a potentially valuable tool to analyze the HER2 status. Polysomy-17 was absent under the CEP17 cutoff ≥3. The existence of HER2 heterogeneity can be discerned in certain HER2-expressed primary mucinous EOC in Taiwanese women.

HER2 amplification and overexpression are significantly correlated in mucinous epithelial ovarian cancer.

HER2 gene amplification and protein over-expression are important factors in predicting clinical sensitivity to anti-HER2 therapies in breast, gastric or gastroesophageal junction cancer patients. The aim of this study was to evaluate the correlation between HER2 gene copy numbers and HER2 protein expressions in mucinous epithelial ovarian cancer (EOC). Of the 49 tissue microarray samples of mucinous EOC, we applied 2010 ToGA trial (Trastuzumab for Gastric Cancer) surgical specimen scoring criteria to analyze the HER2 protein expression by an immunohistochemistry (IHC) test with Dako (Carpenteria, CA), c-erb-B2 antibody, and the HER2 gene amplification by the fluorescence in situ hybridization (FISH) test with Abbott/Vysis PathVysion HER2 DNA Probe Kit (Abbott Molecular Inc., Des Plaines, IA). We achieved a high overall concordance of 97.56% between nonequivocal HER2 results by IHC and FISH tests. In addition, HER2 gene copies before chromosome-17 correction increased significantly in a stepwise order through the negative, equivocal and positive IHC result categories (P<.001), as did the HER2 gene copies after chromosome-17 correction (P<.001). On the other hand, HER2 IHC results correlated significantly with both chromosome-17-uncorrected HER2 gene copy numbers (ρ=0.630, P<.001) and chromosome-17 corrected HER2 gene copy numbers (ρ=0.558, P<.001). We concluded that both chromosome-17 corrected and uncorrected HER2 gene copies correlated significantly with HER2 IHC results. Tests for the HER2 gene copies per tumor cell either before or after correction of chromosome-17 can be applied as a potentially valuable tool to analyze the HER2 status in mucinous EOC.

Primary ovary transitional cell carcinoma after renal transplantation.

Transitional cell carcinoma (TCC) of the urinary tract is the most frequent malignancy following renal transplantation reported in Taiwan. A 67-year-old female underwent bilateral nephrouretectomy and bladder cuff excision because of bilateral hydronephrosis 5 years after cadaveric renal transplantation. The pathologic report was only atrophied kidney. Pelvic sonography and abdominal computed tomography showed a pelvic mass 8 years after transplantation. After gynecological surgery, the pathologic report of the left ovarian tumor was TCC, high grade, stage IIA. The patient then underwent four cycles of postoperative chemotherapy with carboplatin and gemcitabine. TCC of the ovary is a rare, recently recognized subtype of ovarian surface epithelial cancer. We present the first case of primary ovarian TCC following renal transplant.

Five commonly used markers (p53, TTF1, CK7, CK20, and CK34betaE12) are of no use in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study.

BACKGROUND: The choice of appropriate therapeutic plans for primary endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) depends on the tumor's site of origin. Some panels of antibodies help to distinguish primary ECA from EMA. However, unexpected expressions of those markers often exist, which causes this diagnostic dilemma to be still unresolved. In this study, we investigate five commonly used monoclonal antibodies (p53, TTF1, CK7, CK20, and CK34betaE12) to evaluate their potential use in distinguishing between these two gynecologic malignancies. METHODS: A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 35 hysterectomy specimens, including 14 ECA and 21 EMA. Utilizing the avidin-biotin (ABC) technique, tissue array sections were immunostained with the five aforementioned commercially available antibodies. RESULTS: Immunohistochemical (IHC) expressions of p53, TTF1, CK7, CK20, and CK34betaE12 were all nonsignificant (P>0.05) in frequency differences between the immunostaining results (positive vs. negative) in tumors from both the two primary adenocarcinomas (ECA vs. EMA). CONCLUSION: It is still uncertain which markers or panels would be the most appropriate for making diagnoses; hence, exploration of other useful markers, which make a definitive distinction between ECA and EMA merits further studies. This study, however, uncovered that the five commonly used monoclonal antibodies (p53, TTF1, CK7, CK20, and CK34betaE12) are of no beneficial value in distinguishing between primary ECA and EMA.

Progesterone receptor does not improve the performance and test effectiveness of the conventional 3-marker panel, consisting of estrogen receptor, vimentin and carcinoembryonic antigen in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study.

OBJECTIVE: Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) are uterine malignancies that have differing biological behaviors. The choice of an appropriate therapeutic plan rests on the tumor's site of origin. In this study, we propose to evaluate whether PR adds value to the performance and test effectiveness of the conventional 3-marker (ER/Vim/CEA) panel in distinguishing between primary ECA and EMA. METHODS: A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 38 hysterectomy specimens, including 14 ECA and 24 EMA. Tissue microarray (TMA) sections were immunostained with 4 antibodies, using the avidin-biotin complex (ABC) method for antigen visualization. The staining intensity and extent of the immunohistochemical (IHC) reactions were appraised using a semi-quantitative scoring system. RESULTS: The three markers (ER, Vim and CEA) and their respective panel expressions showed statistically significant (p < 0.05) frequency differences between ECA and EMA tumors. Although the additional ancillary PR-marker also revealed a significant frequency difference (p < 0.05) between ECA and EMA tumors, it did not demonstrate any supplementary benefit to the 3-marker panel. CONCLUSION: According to our data, when histomorphological and clinical doubt exists as to the primary site of origin, we recommend that the conventional 3-marker (ER/Vim/CEA) panel is easier, sufficient and appropriate to use in distinguishing between primary ECA and EMA. Although the 4-marker panel containing PR also reveals statistically significant results, the PR-marker offers no supplemental benefit to the pre-existing 3-marker (ER/Vim/CEA) panel in the diagnostic distinction between ECA and EMA.

Scoring mechanisms of p16INK4a immunohistochemistry based on either independent nucleic stain or mixed cytoplasmic with nucleic expression can significantly signal to distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study.

BACKGROUND: Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate 3 different scoring mechanisms of p16INK4a immunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs. METHODS: A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 24 EMAs. Tissue array sections were immunostained with a commercially available antibody of p16INK4a. Avidin-biotin complex (ABC) method was used for antigens visualization. The staining intensity and area extent of the IHC reactions was evaluated using the semi-quantitative scoring system. The 3 scoring methods were defined on the bases of the following: (1) independent cytoplasmic staining alone (Method C), (2) independent nucleic staining alone (Method N), and (3) mean of the sum of cytoplasmic score plus nucleic score (Method Mean of C plus N). RESULTS: Of the 3 scoring mechanisms for p16INK4a expression, Method N and Method Mean of C plus N showed significant (p-values < 0.05), but Method C showed non-significant (p = 0.245) frequency differences between ECAs and EMAs. In addition, Method Mean of C plus N had the highest overall accuracy rate (81.6%) for diagnostic distinction among these 3 scoring methods. CONCLUSION: According to the data characteristics and test effectiveness in this study, Method N and Method Mean of C plus N can significantly signal to distinguish between ECAs and EMAs; while Method C cannot do. Method Mean of C plus N is the most promising and favorable means among the three scoring mechanisms.

Carcinoid tumor of the thymus: a clinicopathologic report of two cases with a review of the literature.

Thymic carcinoid, a tumor with neuroendocrine-derived cells, is extremely rare. Its clinical and pathological features are distinct from other thymic tumors or carcinoids in other organs. The prognosis is poorer compared with other thymic tumors. Herein, we describe two cases with thymic carcinoids that were completely resected and underwent radiotherapy after surgery. The postoperative follow-up periods were 7 years and 7 months. These rare cases are discussed in light of the clinico-pathological picture of thymic carcinoid reported in the literature.