Mucinous and nonmucinous bronchioloalveolar adenocarcinomas have distinct staining patterns with thyroid transcription factor and cytokeratin 20 antibodies.

We studied 14 mucinous and 26 nonmucinous bronchioloalveolar adenocarcinomas (BACs) with thyroid transcription factor (TTF), cytokeratin (CK) 7, CK20, and villin to characterize their staining patterns with these antibodies and identify staining differences between the neoplasms. We also stained 11 mucinous colon adenocarcinomas with the same antibodies to compare their reaction patterns with mucinous BACs. All pulmonary neoplasms were confirmed pulmonary primary BACs. Three (21%) of 14 mucinous neoplasms had weak TTF reactivity in fewer than 25% of neoplastic cell nuclei, and the other 11 (79%) were nonreactive. In contrast, 24 (92%) of 26 nonmucinonus BACs were strongly TTF reactive. Eleven mucinous BACs (79%) had CK20 reactivity in more than 25% of neoplastic cells, whereas only 1 nonmucinous BAC (4%) had reactivity in fewer than 50% of the cells. One mucinous BAC (7%) had villin reactivity in approximately 10% of the neoplastic cells. All mucinous colon adenocarcinomas were diffusely reactive with CK20 and villin. Mucinous and nonmucinous BACs have disparate staining patterns with TTF and CK20. Mucinous BACs are usually TTF nonreactive and CK20 reactive, but nonreactive with villin, which distinguishes them from mucinous colon adenocarcinomas.

[1]  C. di Loreto,et al.  TTF-1 gene expression in human lung tumours. , 1996, European journal of cancer.

[2]  P. Chu,et al.  Cytokeratin 7 and Cytokeratin 20 Expression in Epithelial Neoplasms: A Survey of 435 Cases , 2000, Modern Pathology.

[3]  Dietel,et al.  Thyroid transcription factor‐1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B , 2000, Histopathology.

[4]  M. B. Rosenblatt,et al.  Primary and metastatic bronciolo-alveolar carcinoma. , 1967, Diseases of the chest.

[5]  J. Vandekerckhove,et al.  Villin Function in the Organization of the Actin Cytoskeleton , 1999, The Journal of Biological Chemistry.

[6]  M. Mattéi,et al.  Thyroid nuclear factor 1 (TTF‐1) contains a homeodomain and displays a novel DNA binding specificity. , 1990, The EMBO journal.

[7]  D. Beer,et al.  Unique expression patterns and alterations in the intestinal protein villin in primary and metastatic pulmonary adenocarcinomas , 1998, Molecular carcinogenesis.

[8]  D. M. Geddes,et al.  Bronchioloalveolar carcinoma. , 1987, British medical journal.

[9]  T. Loy,et al.  Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas from colonic adenocarcinomas. , 1994, American journal of clinical pathology.

[10]  J. Whitsett,et al.  Lung Cell-specific Expression of the Murine Surfactant Protein A (SP-A) Gene Is Mediated by Interactions between the SP-A Promoter and Thyroid Transcription Factor-1 (*) , 1995, The Journal of Biological Chemistry.

[11]  J. Whitsett,et al.  Expression of thyroid transcription factor-1(TTF-1) in fetal and neonatal human lung. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[12]  J. Whitsett,et al.  Regulation of surfactant protein gene transcription. , 1998, Biochimica et biophysica acta.

[13]  N. Ordóñez,et al.  Value of thyroid transcription factor-1, E-cadherin, BG8, WT1, and CD44S immunostaining in distinguishing epithelial pleural mesothelioma from pulmonary and nonpulmonary adenocarcinoma. , 2000, The American journal of surgical pathology.

[14]  M. B. Rosenblatt,et al.  Criteria for the histologic diagnosis of bronchogenic carcinoma. , 1967, Diseases of the chest.

[15]  A. Liebow.  Tumors of the lower respiratory tract , 1952 .

[16]  J. Whitsett,et al.  Monoclonal antibody to thyroid transcription factor-1: production, characterization, and usefulness in tumor diagnosis. , 1996, Hybridoma.

[17]  F. Puglisi,et al.  TTF-1 protein expression in pleural malignant mesotheliomas and adenocarcinomas of the lung. , 1998, Cancer letters.

[18]  R. Lauro,et al.  The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis , 1994, Molecular and cellular biology.

[19]  F. Puglisi,et al.  Prognostic value of thyroid transcription factor-1 in primary, resected, non-small cell lung carcinoma. , 1999, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[20]  F. Puglisi,et al.  Immunocytochemical expression of tissue specific transcription factor-1 in lung carcinoma. , 1997, Journal of clinical pathology.

[21]  J. Whitsett,et al.  Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma. , 1999, Human pathology.

[22]  J. Whitsett,et al.  Thyroid Transcription Factor-1 and Cytokeratins 7 and 20 in Pulmonary and Breast Carcinoma , 1998, Acta Cytologica.

[23]  N. Weidner.  The Difficult Diagnosis in Surgical Pathology , 1995 .

[24]  Bacchi Ce,et al.  Distribution and pattern of expression of villin, a gastrointestinal-associated cytoskeletal protein, in human carcinomas: a study employing paraffin-embedded tissue. , 1991 .

[25]  S. E. Kelly,et al.  Transcription of the Lung-specific Surfactant Protein C Gene Is Mediated by Thyroid Transcription Factor 1 (*) , 1996, The Journal of Biological Chemistry.

[26]  Np Wang.  Coordinate expression of cytokeratin 7 and 20 defines unique subsets of carcinomas , 1995 .

[27]  B. Stripp,et al.  Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1. , 1997, Biochimica et biophysica acta.

[28]  A. Gown,et al.  COORDINATE EXPRESSION OF CYTOKERATIN-7 AND CYTOKERATIN-20 DEFINES UNIQUE SUBSETS OF CARCINOMAS , 1995 .

[29]  R. Lauro,et al.  Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. , 1996, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[30]  A. Gown,et al.  Distribution and pattern of expression of villin, a gastrointestinal-associated cytoskeletal protein, in human carcinomas: a study employing paraffin-embedded tissue. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[31]  N. Ordóñez,et al.  Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas. , 2000, Advances in anatomic pathology.

[32]  M. Miettinen,et al.  Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. , 1995, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[33]  A. Gown,et al.  Primary Versus Metastatic Pulmonary Adenocarcinoma: An Immunohistochemical Study Using Villin and Cytokeratins 7 and 20 , 1996 .

[34]  R. Lauro,et al.  The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. , 1991, Development.

[35]  R. Moll,et al.  Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas , 1987, Virchows Archiv. B, Cell pathology including molecular pathology.

[36]  L. Ackerman,et al.  Ackerman's surgical pathology , 1974 .

[37]  R. Wieczorek,et al.  Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets. , 1998, Human pathology.

[38]  M. Wick,et al.  Peripheral pulmonary adenocarcinomas with bronchioloalveolar features: immunophenotypes correlate with histologic patterns. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[39]  E. Mark,et al.  Pulmonary mucinous cystic tumors of borderline malignancy. , 1991, Human pathology.