MASH1: A Specific Immunohistochemical Marker for High Grade Neuroendocrine Tumors of the Lung.
Jaclyn Cappel, Jennifer Findeis-Hosey, Loralee McMahon, Qi Yang, Haodong Xu, Faqian Li. University of Rochester Medical Center, NY
Background: Mammalian/human achaete-scute homolog 1(M/hASH1) is a member of the basic helix-loop-helix family of transcription factors. MASH1 has been shown to play an obligatory role in the development of neuroendocrine cells. No detailed comparative study has been conducted to explore the immunohistochemical utility of MASH1 in distinguishing different types of lung cancers. We investigated the expression of MASH1 in lung cancers including squamous cell carcinoma (SCC), adenocarcinoma (ADC), typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) by immunohistochemistry.
Design: Eighty-eight surgically resected NETL including 38 TCs, 14 ACs, 11 LCNECs and 24 SCLCs as well as tissue microarrays of 183 cases of ADC and 101 cases of SCC of the lung were immunohistochemically studied using a monoclonal antibody against MASH1 (BD Biosciences, clone 24B7.2D11, 1:500). Nuclear staining was considered positive. Staining intensity was graded from 1 to 3 and percentage of tumor cells in each grade was estimated. The product of each intensity scale and the percentage of positive tumor cells for each stain in each case was added to calculate cumulative scores. A case was considered positive if 5% or more tumor cells had positive nuclear staining. Pathologic diagnosis was confirmed with immunohistochemical and mucicarmine stains. A p value of <0.05, as determined by Kruskall-Wallis one way analysis of variance on ranks and Dunn's method using SigmaStat 3.0 (Aspire Software International).
Results: Immunohistochemical studies showed all cases of ADC and SCC were discreetly negative for MASH1. Twenty of 38 TCs (63.2%), 9 of 14 (64.3%) ACs, 8 of 11 (72.7%) LCNECs, and 19 of 24 (79.2%) SCLC were positive for MASH1. TC, AC, and LCNEC had weaker intensity and lower percentage of tumor cells positive for MASH1 than SCLC. The majority of positive TC, AC, and LCNEC demonstrated weak to moderate intensity while SCLC often demonstrated moderate to strong positivity. There were statistically significant differences in median scores between SCLC (170) and low grade NETL, TC (5) and AC (5), but no such difference was detected between LCNEC (40) and SCLC (170).
Conclusions: MASH1 is a specific marker to distinguish NETL from SCC and ADC. Additionally, high grade NETL, especially SCLC have stronger positivity for MASH1 than their low grade counterparts. These findings support that MASH1 is a useful diagnostic marker for segregating SCLC from other NETL and differentiating NETL from non-NETL
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 248, Wednesday Morning