Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation enables accurate assessment of HER2 genomic status in ovarian tumours.

BACKGROUND: Ovarian cancer is a leading cause of gynaecological cancer-related morbidity and mortality. There has been increasing interest in the potential utility of anti-human epidermal growth factor receptor 2 (anti-HER2) agents in the treatment of this disease, with the attendant need to identify suitable predictive biomarkers of response to treatment. AIMS/METHODS: The authors studied the prevalence of HER2 genomic amplification and overexpression in 85 ovarian tumours in the local patient cohort of this study, as well as the concordance rate between immunohistochemistry, fluorescent in situ hybridisation (FISH) and a dual-colour HER2/chromosome 17 centromere chromogenic in situ hybridisation (CISH) assay. RESULTS: The authors identified HER2 genomic amplification and protein overexpression in 35.3% (6/17) and 29.4% (5/17), respectively, of primary ovarian mucinous carcinomas. No other cancer subtypes displayed HER2 amplification or protein overexpression. The authors also found a perfect concordance between FISH and dual-colour CISH analysis (κ coefficient 1.0, p<0.001). CONCLUSION: The results of this study support existing reports that HER2 genomic amplification and protein overexpression are predominantly found in primary ovarian mucinous carcinomas. Given the perfect concordance between the FISH and dual-colour CISH assays and the advantages of CISH over FISH analysis, future clinical trials investigating the use of anti-HER2 therapeutics in ovarian carcinomas should incorporate dual-colour CISH as part of the HER2 status assessment algorithm.

The morphologic spectrum of uterine PEC-cell associated tumors in a patient with tuberous sclerosis.

Perivascular epithelioid cell (PEC) neoplasms are an unusual group of mesenchymal tumors thought to arise from the PEC, which characteristically expresses melanocytic markers with common coexpression of muscle markers. They show a wide morphologic spectrum and have been described in multiple anatomical locations, including the uterus. We report a 59-year-old woman with tuberous sclerosis, initially diagnosed with a uterine malignant mixed müllerian tumor, in whom the hysterectomy specimen also showed 3 other incidental tumors: a subserosal angiomyolipoma consisting of blood vessels of varying caliber, mature adipose tissue, and nests of spindle cells arranged in a perivascular location, a sclerosing PEComa consisting of small nests of clear epithelioid cells present in a background of marked sclerosis centered in the lower uterine segment/endocervix, and diffuse lymphangiomyomatosis involving the endocervix, lower uterine segment, and uterine corpus. This case provides further evidence of a common precursor cell of origin for these lesions.

Diverse phenotypic profile of uterine tumors resembling ovarian sex cord tumors: an immunohistochemical study of 12 cases.

BACKGROUND: Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare neoplasms thought to be of putative endometrial stromal origin and solely composed of sex cord elements. Our study aimed to delineate the immunophenotype of these tumors and to verify whether their morphology reflects true sex cord-like differentiation. DESIGN: Representative paraffin blocks from 12 UTROSCTs were selected after confirmation of the diagnosis. Cords and/or trabeculae were seen in all tumors, whereas tubules, diffuse areas, and a retiform pattern were present in 9, 6, and 2 cases, respectively. Tumors were stained for sex cord (inhibin, calretinin, WT1, and melan-A), epithelial (KL1 and epithelial membrane antigen), and smooth muscle markers (smooth muscle actin, desmin, smooth muscle myosin heavy chain, h-caldesmon, and histone deacetylase-8), CD10, HMB45, S100, and CD117. Intensity and percentage of staining were recorded. RESULTS: Six out of 12 tumors were positive for sex cord markers (inhibin 3 of 12, calretinin 4 of 12, WT1 4 of 12, and melan-A 3 of 11) with 4 tumors coexpressing more than one marker. Half of the UTROSCTs showed positivity for KL1, with 2 tumors coexpressing epithelial membrane antigen. All but one tumor expressed one or more smooth muscle markers, with smooth muscle actin, desmin and histone deacetylase-8 being most commonly expressed. CD10 was positive in 6 of 12 tumors, CD117 in 4 of 12, and S100 in 2 of 11 tumors, whereas HMB45 was negative in 11 tumors tested. CONCLUSIONS: UTROSCTs have a diverse immunohistochemical profile often coexpressing sex cord, epithelial, and smooth muscle markers. The expression of smooth muscle markers in these tumors does not imply a smooth muscle origin as endometrial and sex cord stromal tumors are not infrequently positive for these markers. Positivity for sex cord markers supports a true sex cord/steroid phenotype. Although the immunohistochemical profile of these tumors overlaps with that of endometrial stromal tumors with sex cord-like differentiation as well as ovarian sex cord stromal tumors, the origin of UTROSCT remains uncertain.