Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma
ABSTRACT 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.
[Show abstract] [Hide abstract]
ABSTRACT: Gastric metastases from lung adenocarcinoma are rare. Because gastric metastasis grossly resembles advanced gastric cancer, it is difficult to diagnose gastric metastasis especially when the histology of the primary lung cancer is adenocarcinoma. We describe a case of gastric metastasis from primary lung adenocarcinoma mimicking Borrmann type IV primary gastric cancer. A 68-year-old man with known lung adenocarcinoma with multiple bone metastases had been experiencing progressive epigastric pain and dyspepsia over one year. Esophagogastroduodenoscopy revealed linitis plastica-like lesions in the fundus of the stomach. Pathologic examination revealed a moderately differentiated adenocarcinoma with submucosal infiltration. Positive immunohistochemical staining for thyroid transcription factor-1 (TTF-1) and napsin A (Nap-A) confirmed that the metastasis was pulmonary in origin. The patient had been treated with palliative chemotherapy for the lung cancer and had lived for over fifteen months after the diagnosis of gastric metastasis. Clinicians should be aware of the possibility of gastric metastasis in patients with primary lung adenocarcinoma, and additional immunohistochemical staining for Nap-A as well as TTF-1 may help in differentiating its origin.
[Show abstract] [Hide abstract]
ABSTRACT: Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically. Formalin fixed paraffin embedded (FFPE) lung samples featuring inflammation were obtained with a rat quartz instillation model, and neoplastic lesions, hyperplasias and adenomas, were obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz instillation model, male 10-week old F344 rats were exposed by intratracheal instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was initiated by DHPN in drinking water for 2 weeks, and the animals were then sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas, were observed with DHPN, and inflammation was observed with quartz. The expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP-B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A and SP-D were observed in mucus or exudates in inflammatory alveoli. These results suggest the possibility that SP-B and SP-C are related to lung tumorigenesis.Journal of Toxicologic Pathology 10/2014; 27(3-4):175-82. DOI:10.1293/tox.2014-0020 · 0.94 Impact Factor
Diagnostic Pathology 12/2015; 10(1). DOI:10.1186/s13000-015-0242-z · 2.41 Impact Factor