Bishop JA, Sharma R, Illei PB. Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma

Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Human pathology (Impact Factor: 2.77). 10/2009; 41(1):20-5. DOI: 10.1016/j.humpath.2009.06.014
Source: PubMed


Recent advances in the treatment of pulmonary adenocarcinoma have increased the need for accurate typing of non-small cell carcinomas. Immunohistochemistry for thyroid transcription factor-1 is widely used in the diagnosis of pulmonary adenocarcinomas because it marks approximately 75% of lung adenocarcinomas and is negative in most squamous cell carcinomas and adenocarcinomas of other organs. Napsin A is an aspartic proteinase involved in the maturation of surfactant protein B. It is detected in the cytoplasm of type 2 pneumocytes and alveolar macrophages and is a putative marker for pulmonary adenocarcinomas. We performed immunohistochemistry for napsin A and thyroid transcription factor-1 using tissue microarrays of 95 adenocarcinomas, 48 squamous cell carcinomas, 6 neuroendocrine tumors of the lung, as well as 5 colonic, 31 pancreatic, and 17 breast adenocarcinomas, 38 malignant mesotheliomas, 118 renal cell carcinomas, and 81 thyroid tumors. The tissue microarrays also included 15 different benign tissues. Pulmonary adenocarcinomas were napsin A positive in 79 (83%) of 95 cases compared with 69 (73%) of 95 cases that were thyroid transcription factor-1 positive. There were 13 napsin A-positive/thyroid transcription factor-1-negative and 2 thyroid transcription factor-1-positive/napsin A-negative tumors, increasing the number of cases that were positive with at least one of the markers to 81 (85%) of 95. The limited number of neuroendocrine tumors tested was napsin A negative. All squamous cell carcinomas, adenocarcinomas of the colon, pancreas and breast, and mesotheliomas were negative for both markers. Of the renal tumors, napsin A was positive in most of papillary renal cell carcinomas (79%), about one third (34%) of clear cell renal cell carcinomas, and in a single case of chromophobe renal cell carcinoma (3%). In the thyroid, only 2 cases of papillary thyroid carcinoma (5%), both with tall cell morphology, were positive for napsin A, whereas all other papillary and follicular carcinomas were negative. As expected, all renal tumors were thyroid transcription factor-1 negative, and all thyroid tumors, except for one papillary carcinoma, were thyroid transcription factor-1 positive. Napsin A is a sensitive marker for pulmonary adenocarcinoma and is also expressed in a subset of renal cell carcinomas, particularly of the papillary type, as well as in rare cases of papillary thyroid carcinomas. The combined use of napsin A and thyroid transcription factor-1 results in improved sensitivity and specificity for identifying pulmonary adenocarcinoma in primary lung tumors and in a metastatic setting.

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    • "To further characterize these tumors, we stained the tissues with two antibody combinations used by pathologists to differentiate lung adenocarcinomas (Napsin A + TTF1) [29] and squamous cell carcinomas (p63+CK5) [30]. These two sets of antibodies were observed to stain different areas of the parental tumor and all 8 clonally derived xenografts and metastases (Figure 2 A, Figure S1). "
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    • "In 5 of 10 cases when immunoperoxidase studies were performed in our series we were able to identify the primary site of metastatic cancers in the PPS. The often helpful immunoperoxidase stains in this regard are cytokeratins 7 and 20,15 DPC4 (expression is lost in 55% of pancreatic adenocarcinomas),16 CDX-2 and/or villin (usually positive in intestinal carcinomas, especially colonic),15 and markers like HMB-45/S-100 protein,15 TTF-1/napsin-A,17 HepPar-1,15 RCC/PAX-2,15 and inhibin (relatively specific for melanoma, carcinomas of the lung, liver, kidney, and the adrenals, respectively).15 "
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    • "A promising addition on immunohistochemical panel for identifying metastases from lung cancer could be the Napsin A, an aspartic proteinase detected in type 2 pneumocytes and alveolar macrophages, and putative marker for pulmonary adenocarcinomas. Indeed, Napsin A is useful for distinguishing primary lung adenocarcinoma from adenocarcinomas of other organs at primary and metastatic sites [20], and, in particular, the combined use of Napsin A and TTF-1 increased sensitivity and specificity for identifying lung origin in the setting of a metastatic adenocarcinoma [21]. "
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