Expression of neuroendocrine markers in non-neuroendocrine endometrial carcinomas

Neuroendocrine (NE) tumours are uncommon in the gynecological tract. In addition to their histological features, what defines NE carcinoma is the expression of markers such as chromogranin, synaptophysin and neural cell adhesion molecule (CD56) by immunohistochemistry (IHC). Although limited data have demonstrated that some high-grade uterine tumours may focally express these markers, the incidence of such labelling in endometrial carcinomas in general is not well known. The goal of this study was to characterise the expression of NE markers in a cohort of endometrial carcinomas. We searched our institutional surgical pathology database for hysterectomy specimens containing endometrial carcinomas. Cases demonstrating classic morphological features of NE carcinomas were excluded. IHC for synaptophysin, chromogranin and CD56 was performed in whole-tissue sections of formalin-fixed, paraffin-embedded (FFPE) tumours. Thyroid transcription factor 1 (TTF-1) was also included, given its positivity in a subset of small cell carcinomas. Marker expression was graded based on percentage of positive tumour cells (0, not detected; 1, 1-25%; 2, 25-50%; 3, >50%). Chi-square was used for statistical analysis and significance was set at p<0.05. In total, 71 carcinomas of endometrioid (EMCA; 26 cases), serous (20), clear cell (12), undifferentiated (2) and dedifferentiated (1) histologies were obtained, as well as 10 carcinosarcomas. The majority expressed one or more NE markers (47/71; 66%), with most positive cases showing focal (1+) staining of a single marker. Significantly more tumours stained positive for CD56 than synaptophysin (58% vs 7%, p<0.01). Clear cell carcinomas were the least likely to express any NE marker (4/12; 33%), whereas serous carcinomas (80%) and carcinosarcomas (100%) were the most likely. CD56 labelling was seen in 9/10 carcinosarcomas, in both epithelial (7/9) and mesenchymal (5/9) elements. A slightly greater proportion of non-endometrioid histological types stained positive for TTF-1 compared with endometrioid type (31% vs 12%, p=0.06). Immunohistochemical expression of NE markers is relatively common in endometrial carcinomas that lack classic NE histology. The most frequent pattern encountered in our study was focal (1-25%) labelling of a single marker. Synaptophysin appeared reliably negative, while CD56 was commonly present in non-NE histology. Clear cell carcinomas tend to be consistently negative, whereas carcinosarcomas and serous carcinomas frequently express at least one marker. Awareness of these data may help to avoid misdiagnosis of a neuroendocrine carcinoma in limited samples.