Expression of Squamous Cell Carcinoma Markers and Adenocarcinoma Markers in Primary Pulmonary Neuroendocrine Carcinomas

Abstract

Recent clinical trials have revealed that accurate histologic typing of non-small cell lung cancer is essential. Until now, squamous cell carcinoma (SQC) and adenocarcinoma (ADC) markers have not been thoroughly analyzed for pulmonary neuroendocrine carcinomas (NECs). We analyzed the expression of 8 markers [p63, cytokeratin (CK) 5/6, SOX2, CK7, desmocollin 3, thyroid transcription factor-1 (8G7G3/1 and SPT24), and napsin A] in 224 NECs. SOX2 (76.2%) had the greatest expression for NECs. CK5/6 (1.4%), desmocollin 3 (0.5%), and napsin A (0%) were expressed less or not at all in NECs. Although our investigated markers have been reported useful for differentiating between SQC and ADC, some of them were also present in a portion of pulmonary NECs. In our study, CK5/6 and desmocollin 3 were highly specific markers for SQC, and napsin A was highly specific for ADC. These markers are recommended for diagnosis of poorly differentiated non-small cell lung cancer.

Desmocollin-3 and Cancer

“…Sensitivity of DSC3 for squamous NSCLC is 93.2% in large cohort of 426 but drops to 59% in poorly differentiated squamous NSCLC (Table 1). DSC3 expression in NSCLC is also not related to stage or histologic grade [17] of a disease [46].…”

Original paper Morphological and immunohistochemical profile of pancreatic neuroendocrine neoplasms

“…The association with p53 (p < 0.001) and E-cadherin (p = = 0.009) was also indirect evidence of aggressive features. Previously, expression of p63 was reported in pulmonary non-small cell neuroendocrine carcino-mas [99] and neuroendocrine carcinomas of the head and neck [100] in studies of diagnostic value.…”

Utility of Immunohistochemistry in the Diagnosis of Pleuropulmonary and Mediastinal Cancers: A Review and Update

“…Napsin A is absent in TC, AC, and SCLC, but about 10% of LCNECs have been found to be strongly and diffusely positive. 22 Positive staining for sex-determining region Y box 2 (SOX2) is found in about 72% of NECs, 32% of TCs, 81% of LCNECs, and 87% of SCLCs. The positive staining pattern of SOX2 can be either diffusely or focally positive.…”

“…3,6,7,[11][12][13][14][15][16] A subset of cases may even focally express neuroendocrine markers, including chromogranin (9%) and synaptophysin (15%). 7,22 Patterns of multi-messenger RNA expression in some LCCs may match those in differentiated SCC or ADC. Adenocarcinoma-associated mutations (EGFR, KRAS, BRAF, MAP2K1/ MEK1, neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS], and ERBB2/HER2, as well as ALK) or SCCassociated mutations (phosphoinositide 3 kinase [PI3K] and AKT1) may be found in LCC, and tend to segregate with an IHC profile associated with the corresponding tumor subtype.…”

“…It is worth noting that approximately 8% of SCC cases were positive for 1 of 3 neuroendocrine markers (CD56, synaptophysin, and chromogranin) and about 12% of ADC cases were positive for 2 of 3 of the markers. 22 3.0 cm in size) or lacks a circumscribed border, with miliary spread to adjacent lung parenchyma. Histologically, the tumor shows invasion of greater than 0.5 cm, characterized by scattered, well-differentiated tumor cells in large mucin pools and growth along alveolar walls.…”