Immunohistochemical Profile of Resected Large Cell Carcinoma of the Lung
Jianwu Xie, Yulin Liu, Jan F Silverman. Allegheny General Hospital, Pittsburgh, PA
Background: By definition, large cell carcinoma (LCC) is an undifferentiated non-small cell carcinoma that lacks architectural and cytologic features of adenocarcinoma (ACA) or squamous carcinoma (SCA) based on histologic examination. Although it should not change the diagnosis, LCC can express immunohistochemical (IHC) markers for ACA or SCA. In addition, the immunophenotypic profile of a LCC may potentially be helpful in directing additional molecular analysis that can influence therapeutic options. Accordingly, we performed an immunophenotypic analysis of previously diagnosed LCC.
Design: 34 cases of LCC diagnosed from 2000 to 2008 were selected. None of these cases had morphologic features of specific subtypes of LCC or large cell neuroendocrine carcinoma (LCNEC). All diagnosis was based on the absence of either glandular or squamous differentiation in the H&E examination and none showed a small cell carcinoma component. Eight cases previously underwent limited IHC studies for neuroendocrine markers and six cases had IHC work-up to either separate a primary lung carcinoma from a metastatic carcinoma or to further classify the primary LCC. Five cases were stained with mucicarmine. A contemporary IHC panel for classification of non-small cell carcinoma consisting of p63, p40, CK5/6, Napsin-A, TTF-1, chromogranin, and synaptophysin was performed on all cases. The results of the IHC stains were independently graded semi-quantitatively on a scale of 0-2+ positivity and 1-4+ for range of percentage of positive cells (1-25%, 26-50%, 51-75% and 75-80%) by two pathologists. The staining results of LCC were subject to cluster analysis. The control group consisted of 3 cases each of ACA, SCA and LCNEC.
Results: Immunohistochemical staining for p63, p40, CK5/6, chromogranin, synaptophysin, Napsin-A and TTF-1 showed 12%, 24%, 6%, 9%, 15%, 53% and 68% positively, respectively. Based on cluster analysis, we were able to place LCC into three immunophenotypical groups demonstrating IHC profiles of ACA, SCA or LCNEC in 56% (9/34), 12% (4/34) and 6% (2/34), respectively. There were 9/34 (26%) LCC which did not express any of the IHC markers. We found that p40 staining intensity was weaker with fewer cells positive compared to p63 in the same case.
Conclusions: Using a contemporary IHC panel, 74% of LCC expressed immunophenotypic profiles of ACA, SCA, or LCNEC. 56% of LCC demonstrated immunophenotype expression for ACA, 12% for SCA and 6% for LCNEC. IHC profiles of LCC may potentially be helpful in directing further molecular analysis for targeted therapy.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 291, Wednesday Afternoon