TTF-1, Cytokeratin 7, 34bE12, and CD56/NCAM Immunostaining in the Subclassification of Large Cell Carcinomas of the Lung

Abstract

We selected a 4-stain immunopanel including thyroid transcription factor (7ITF)-], cytokeratin (CK)7, 34betaE12, and CD56/neural cell adhesion molecule(NCAM) to subclassify a series of 45 pulmonary large cell carcinomas (LCCs) on bronchial biopsy. All cases consisted of a large tumor cell proliferation with abundant cytoplasm, vesicular nuclei, and prominent nucleoli. Immunohistochemically, 27 tumors (60%)were subclassified as adenocarcinoma (7TF-1 +/CK7+,24; CK7+ only, 3), 10 (22%) as squamous cell carcinoma (34betaE12+ only), and 4 (9%) as LCC with neuroendocrine differentiation (CD56+, variably stained with TTF-I and CK7, 34betaE12-). In 4 cases, the tumors coexpressed CK7 and 34betaE12 (3 cases) or were completely unstained (I case). Surgically resected tumors matched exactly with the corresponding original biopsy specimens in 21 of 23 cases; consistent CD56 expression was a reliable marker in confirming a diagnosis of large cell neuroendocrine carcinoma even on biopsy. Our results suggest that the proposed 4-stainset of commercially available markers might help subclassify LCC even in small biopsy material, validating expression-profiling studies aimed at lung cancer classification and permitting more consistent patient enrollment for trials with targeted treatments.

Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens

“…7 Several recent studies showed that immunostains (and previously electron microscopy 42 ) can reveal the line of differentiation as adenocarcinoma vs squamous cell carcinoma in the majority of large cell carcinomas. 26,36,43,44 The proposed TTF-1/p63 algorithm could be used to determine biological identity within the large cell carcinoma, but this needs further study.…”

Co-Activation of Epidermal Growth Factor Receptor and c-MET Defines a Distinct Subset of Lung Adenocarcinomas

“…29,30 Both of these gene families have been used in numerous histopathological studies to characterize various types of cancer, including lung adenocarcinomas. 31,32,33 Noting this, we reasoned that expression data on these families, together with data on TTF-1 expression, would provide fundamental information on the properties of lung adenocarcinoma cells. Toward this end, we extracted expression profile data for the cytokeratin and MUC family genes and examined the relative expression levels of these genes in the cell lines.…”

Pulmonary Large Cell Carcinoma Lacking Squamous Differentiation Is Clinicopathologically Indistinguishable From Solid-Subtype Adenocarcinoma

“…As a result, LCC contains a heterogeneous mix of entities, which complicates any potential characterization studies or clinical trials. In addition to gene expression-based approaches, [11][12][13][14][15][16][17] multiple studies [18][19][20][21][22][23][24][25][26][27] have shown that LCC can be reclassified as ADC, SQC, or large cell neuroendocrine carcinoma by immunohistochemistry. The widespread use of immunohistochemistry in diagnostic practice may explain the decreasing incidence of LCC.…”