Achaete-Scute Homolog-1 (ASH1) as a Marker of Poorly Differentiated Neuroendocrine Carcinomas of Different Sites: A Validation Study Using Immunohistochemistry and Quantitative RT-PCR on 335 Cases
Stefano La Rosa, Alessandro Marando, Gaia Gatti, Ida Rapa, Marco Volante, Mauro Papotti, Fausto Sessa, Carlo Capella. Ospedale di Circolo, Varese, Italy; University of Insubria, Varese, Italy; University of Turin, Turin, Italy
Background: Neuroendocrine carcinomas (NECs) show overlapping morphologic and immunohistochemical features independently of the site of origin, so the identification of the primary site, when diagnosed as metastases of unknown origin, may be problematic. The distinction of NECs from differentiated neuroendocrine tumors (NETs) is generally easy on morphological ground in surgical material, but it may be difficult on small biopsy specimens. The diagnostic usefulness of different transcription factors, including TTF1 and CDX2, as site-specific markers or as discriminating markers between NECs and NETs has been studied with results not conclusive and sometimes contradictory. In this respect, the role of the transcription factor ASH1, known to be involved in neuroendocrine cell differentiation of the lung, has been poorly investigated.
Design: We investigated using immunohistochemistry and quantitative RT-PCR the expression of ASH1 in 335 neuroendocrine neoplasms of different sites to check its possible utility as a diagnostic marker. 194 NECs (34 lung, 12 head and neck, 83 digestive, 42 urogenital, and 23 skin cases) and 141 NETs (107 lung, 24 gut, and 10 pancreatic) were studied.
Results: High concordance between immunohistochemical and molecular findings was observed. ASH1 expression was identified in 28/34 (82%) lung NECs, but also in 65/160 (41%) NECs elsewhere located, including gastric, colonic, prostatic, urinary bladder and skin NECs. The sensitivity and specificity of ASH1 in identifying lung NECs were 83.2% and 59.4%, respectively. ASH1 was not detected in any gastroenteropancreatic NET but was found in a minor population of tumor cells of 11/107 (10%) lung carcinoids. The sensitivity and specificity of ASH1 in distinguishing lung NECs from NETs were 82.4% and 89.7%, respectively. The sensitivity and specificity of ASH1 in distinguishing extrapulmonary NECs from NETs were 40.6% and 100%, respectively.
Conclusions: Our data suggest that ASH1 is not a site-specific marker to identify lung NECs. However, ASH1 may be proposed as a diagnostic marker of poor differentiation and can be used to differentiate NECs from NETs in difficult cases.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 66, Wednesday Afternoon