TY - JOUR
T1 - Differential distribution of the neuron-associated class III β-tubulin in neuroendocrine lung tumors
AU - Katsetos, Christos D.
AU - Kontogeorgos, George
AU - Geddes, Jennian F.
AU - Herman, Mary M.
AU - Tsimara-Papastamatiou, Hera
AU - Yu, Yunxia
AU - Sakkas, Lazaros I.
AU - Tsokos, Maria
AU - Patchefsky, Arthur S.
AU - Ehya, Hormoz
AU - Cooper, Harry S.
AU - Provencio, Javier
AU - Spano, Anthony J.
AU - Frankfurter, Anthony
PY - 2000
Y1 - 2000
N2 - Objective. To study the immunoreactivity profile of the neuron- associated class III β-tubulin isotype (β III) in epithelial lung tumors. Design. - One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-β III mouse monoclonal antibody (TuJ1) and an anti-β III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. Results. - In the fetal airway epithelium, β III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. β III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, β III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of β III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. β III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of β III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. Conclusions. - In the context of neuroendocrine lung tumors, β III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, β III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, β III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of β III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.
AB - Objective. To study the immunoreactivity profile of the neuron- associated class III β-tubulin isotype (β III) in epithelial lung tumors. Design. - One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-β III mouse monoclonal antibody (TuJ1) and an anti-β III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. Results. - In the fetal airway epithelium, β III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. β III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, β III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of β III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. β III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of β III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. Conclusions. - In the context of neuroendocrine lung tumors, β III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, β III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, β III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of β III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.
KW - Adult
KW - Amino Acid Sequence
KW - Animals
KW - Antibodies
KW - Antibodies, Monoclonal
KW - Carcinoid Tumor/pathology
KW - Carcinoma, Non-Small-Cell Lung/pathology
KW - Carcinoma, Small Cell/pathology
KW - Child
KW - Fetus
KW - Humans
KW - Infant
KW - Lung Neoplasms/pathology
KW - Lung/cytology
KW - Mice
KW - Molecular Sequence Data
KW - Neuroendocrine Tumors/pathology
KW - Peptide Fragments/chemistry
KW - Rabbits
KW - Respiratory Mucosa/cytology
KW - Tubulin/analysis
UR - http://www.scopus.com/inward/record.url?scp=12944255850&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000086508900012&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.5858/2000-124-0535-DDOTNA
DO - 10.5858/2000-124-0535-DDOTNA
M3 - Article
C2 - 10747310
SN - 0003-9985
VL - 124
SP - 535
EP - 544
JO - Archives of Pathology and Laboratory Medicine
JF - Archives of Pathology and Laboratory Medicine
IS - 4
ER -