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
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.
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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)  and squamous cell carcinomas (p63+CK5) . 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). "
ABSTRACT: There is increasing evidence that many solid tumors are hierarchically organized with the bulk tumor cells having limited replication potential, but are sustained by a stem-like cell that perpetuates the tumor. These cancer stem cells have been hypothesized to originate from transformation of adult tissue stem cells, or through re-acquisition of stem-like properties by progenitor cells. Adenosquamous carcinoma (ASC) is an aggressive type of lung cancer that contains a mixture of cells with squamous (cytokeratin 5+) and adenocarcinoma (cytokeratin 7+) phenotypes. The origin of these mixtures is unclear as squamous carcinomas are thought to arise from basal cells in the upper respiratory tract while adenocarcinomas are believed to form from stem cells in the bronchial alveolar junction. We have isolated and characterized cancer stem-like populations from ASC through application of selective defined culture medium initially used to grow human lung stem cells. Homogeneous cells selected from ASC tumor specimens were stably expanded in vitro. Primary xenografts and metastatic lesions derived from these cells in NSG mice fully recapitulate both the adenocarcinoma and squamous features of the patient tumor. Interestingly, while the CSLC all co-expressed cytokeratins 5 and 7, most xenograft cells expressed either one, or neither, with <10% remaining double positive. We also demonstrated the potential of the CSLC to differentiate to multi-lineage structures with branching lung morphology expressing bronchial, alveolar and neuroendocrine markers in vitro. Taken together the properties of these ASC-derived CSLC suggests that ASC may arise from a primitive lung stem cell distinct from the bronchial-alveolar or basal stem cells.PLoS ONE 12/2013; 8(12):e79456. DOI:10.1371/journal.pone.0079456 · 3.23 Impact Factor
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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 "
ABSTRACT: The pancreas is surrounded by soft tissue known as the peripancreatic space (PPS). Pathologic lesions of the PPS are infrequent and have only rarely been reported in the cytopathology literature. A retrospective review of cytopathology files at two large institutions revealed 42 cases of PPS lesions obtained by transabdominal fine needle aspiration (FNA) or endoscopic ultrasound-guided FNA over a 16-year period. Clinicoradiologic findings and follow-up information were also reviewed. Patients ranged in age from 23-83 years (mean, 60 years) with an equal gender distribution. The major clinical presentations included pain, jaundice, nausea/vomiting, and abnormal liver enzymes. Radiographic characteristics included lymphadenopathy and cystic/solid soft tissue masses with a size range of 1.5 to 8 cm. Cytologically, 4 (9.5%) cases were nondiagnostic, 9 (21.5%) were diagnosed as benign, 4 (9.5%) were atypical or suspicious for cancer, and 25 (59.5%) were malignant. Six of 25 (24%) patients had metastasis of a prior known malignancy. FNA of PPS masses is a rare occurrence. The majority of lesions are metastatic carcinomas from a variety of primary sites. Flow cytometry and immunoperoxidase studies are useful adjuncts to determine the tumor origin. The sensitivity of PPS aspiration for a malignant diagnosis is 90% with a positive predictive value of 100%.The Korean Journal of Pathology 06/2013; 47(3):258-64. DOI:10.4132/KoreanJPathol.2013.47.3.258 · 0.17 Impact Factor
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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 , 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 . "
ABSTRACT: Metastatic neoplasms to the ovary often cause diagnostic problems, in particular those large ovarian masses mimicking primary tumors. Most of these tumors arise from digestive system or breast, while 37-year-old woman diagnosed as right adnexal complex mass, with a subpleural nodule in the apical part of the left lower lobe, at preoperative chest computed tomography scan. The patient underwent total abdominal hysterectomy with right salpingo-oophorectomy (ovarian mass 220 × 200 mm), total omentectomy, left ovarian biopsy, peritoneal random biopsies, and peritoneal washings for cytology. Pathologic and immunohistochemical examination of ovarian specimen suggested morphology and expression of metastatic lung adenocarcinoma with an intense positivity for Thyroid Transcriptional Factor-1 (TTF-1) and Cytokeratin 7 (CK7) staining. Fine needle biopsy of the lung nodule found epithelioid like malignant cells, confirming the diagnosis of an ovarian metastasis from a primary lung cancer. This report focused on the clinical and pathologic diagnostic challenge of distinguishing secondary from primary ovarian neoplasms. Issues on useful immunohistochemical stains are also discussed.Journal of Ovarian Research 05/2013; 6(1):34. DOI:10.1186/1757-2215-6-34 · 2.43 Impact Factor