A panel of four immunohistochemical markers (CK7, CK20, TTF-1, and p63) allows accurate diagnosis of primary and metastatic lung carcinoma on biopsy specimens

Abstract

Accurate classification of lung cancer, as well as the differentiation between primary and metastatic carcinoma to the lung, mostly performed on biopsy or fine needle aspiration specimens, is critical for decisions on therapy and for determining prognosis. The limited amount of biopsy material available for morphological assessment has stimulated attempts to improve diagnostic accuracy through the use of immunohistochemistry (IHC), but an optimal IHC diagnostic algorithm has not been firmly established. We evaluated, on a retrospective series of biopsy specimens, the performance of a four-antibody IHC panel for accurate subclassification of non-small cell lung carcinoma (NSCLC) and for identification of metastatic carcinoma. Tumor morphology was assessed and IHC for CK7, CK20, TTF-1, and p63 was performed according to a two-step algorithm. Matched resection specimens served as gold standard and were compared with the corresponding biopsy. Of 443 biopsy specimens studied, 325 were diagnosed as primary carcinoma of the lung, 198 (44.7 %) as adenocarcinoma, 9 (2 %) as possibly adenosquamous carcinoma, 127 (28.7 %) as squamous cell carcinoma, and 40 (9 %) as NSCLC not further classifiable. Ten cases (2.3 %) were classified as adenocarcinoma of unknown origin and 58 (13 %) as metastasis. Importantly, of the primary lung adenocarcinomas, 35 (17.7 %) had been considered on clinical grounds as a metastasis from a previously diagnosed primary tumor. Of the 55 cases submitted to surgical resection in 47 (85.5 %) the biopsy diagnosis was confirmed, revealing substantial agreement (κ value = 0.757). Our two-step approach allows for accurate subclassification of NSCLC and also to distinguish between primary lung adenocarcinoma and metastasis, notably of colorectal adenocarcinoma, with crucial implications for appropriate patient management.

Predictive value of CK20 in evaluating the efficacy of treatment and prognosis after surgery for colorectal cancer

“…Although modern cancer therapy can effectively control progression of colorectal carcinoma, there is a trend towards increased mortality (Montezuma et al, 2013). Current techniques for the evaluation of colorectal cancer include pathological examination, tumor marker level measurement, and observation of clinical symptoms, although they are all associated with inherent limitations that leads to difficulty in detecting early stage tumors and lymph node metastases (Eisenberg-Lerner et al, 2009;Littman and Rudensky, 2010;Pavlidis and Pentheroudakis, 2012).…”

Large-cell neuroendocrine carcinoma (LCNEC) without pulmonary symptoms diagnosed in a cutaneous metastasis: A case report

“…The patient had extensive brain and bone metastasis with lesions in the left pulmonary hilum and left lower lobe, consistent with the manifestation of lung cancer [16]. Furthermore, positive TTF-1 (Thyroid Transcription Factor-1) and negative CK20 (Cytokeratin 20) stains strongly indicated that the primary site of the tumor was the pulmonary system [17]. TTF-1 is a nuclear transcription factor that regulates cell growth and differentiation in thyroid, lung, and selected brain tissue [18].…”

Pulmonary enteric adenocarcinoma with pancreatic metastasis: A case report

“…Inamura et al (3) identified that TTF-1 and CK7 were all negative in the 14 samples of MCC; however, CDX2 and CK20 were markedly positive in 12 cases. Montezuma et al (22) performed IHC detection in 25 cases of MCC and 198 cases of PLA, revealing that all MCC cases were positive for CK20, but negative for TTF-1, and CK7 was negative or weakly expressed; all PLA cases were strongly positive for TTF-1, a number were positive for CK7, and only a limited number were weakly positive for p63. TTF-1, which belongs to the NK-2 homeobox family, is positive in PLA, but negative in MCC, therefore it is recognized as the best single stain for PLA (23).…”