Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas

Kazuo Yashima, Leslie A. Litzky, Larry Kaiser, Thomas Rogers, Stephen Lam, Ignacio I. Wistuba, Sara Milchgrub, Sudhir Srivastava, Mieczyslaw A. Piatyszek, Jerry W. Shay, Adi F. Gazdar

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Abstract

To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat amplification protocol assay (131 samples) or by a radioactive in situ hybridization method for expression of the RNA component of human telomerase (hTR; 74 samples). A subset of samples was assayed by both methods, and the correlation was excellent (3b of 36; 83%). With the exception of a carcinoid tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to strongly positive for both hTR and telomerase activity, except for foci of keratinization in squamous cell carcinomas. Telomerase positivity, with weak enzyme activity and/or low hTR expression, was present in basal epithelial cells of large bronchi, both histologically normal (26%) and hyperplastic (71%), and in 23% of peripheral lung samples (in epithelium of small bronchi and bronchiolus or lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia, and CIS) were associated with telomerase dysregulation. Dysregulation in preneoplasia was manifested in three ways: almost all such lesions expressed hTR, although enzyme activity levels were several-fold lower than in the corresponding invasive tumors; cells throughout these multilayered processes expressed hTR; and intense, focal up- regulation of hTR occurred in CIS foci in the vicinity of invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia (possible precursor lesions for peripheral adenocarcinomas) were negative. Our studies demonstrate that dysregulation of telomerase occurs early in the multistage pathogenesis of bronchogenic lung carcinomas and that intense focal localized hTR expression in CIS may indicate imminent invasion.

Original languageEnglish (US)
Pages (from-to)2373-2377
Number of pages5
JournalCancer Research
Volume57
Issue number12
StatePublished - Jun 15 1997

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Respiratory Mucosa
Telomerase
Carcinoma in Situ
Carcinoma
Lung
Bronchi
Squamous Cell Carcinoma
Enzymes
Alveolar Epithelial Cells
Neoplasms
Bronchogenic Carcinoma
Carcinoid Tumor
Metaplasia
Hyperplasia
In Situ Hybridization
Lung Neoplasms
Adenocarcinoma
Up-Regulation
Epithelium
Epithelial Cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Yashima, K., Litzky, L. A., Kaiser, L., Rogers, T., Lam, S., Wistuba, I. I., ... Gazdar, A. F. (1997). Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. Cancer Research, 57(12), 2373-2377.

Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. / Yashima, Kazuo; Litzky, Leslie A.; Kaiser, Larry; Rogers, Thomas; Lam, Stephen; Wistuba, Ignacio I.; Milchgrub, Sara; Srivastava, Sudhir; Piatyszek, Mieczyslaw A.; Shay, Jerry W.; Gazdar, Adi F.

In: Cancer Research, Vol. 57, No. 12, 15.06.1997, p. 2373-2377.

Research output: Contribution to journalArticle

Yashima, K, Litzky, LA, Kaiser, L, Rogers, T, Lam, S, Wistuba, II, Milchgrub, S, Srivastava, S, Piatyszek, MA, Shay, JW & Gazdar, AF 1997, 'Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas', Cancer Research, vol. 57, no. 12, pp. 2373-2377.
Yashima K, Litzky LA, Kaiser L, Rogers T, Lam S, Wistuba II et al. Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. Cancer Research. 1997 Jun 15;57(12):2373-2377.
Yashima, Kazuo ; Litzky, Leslie A. ; Kaiser, Larry ; Rogers, Thomas ; Lam, Stephen ; Wistuba, Ignacio I. ; Milchgrub, Sara ; Srivastava, Sudhir ; Piatyszek, Mieczyslaw A. ; Shay, Jerry W. ; Gazdar, Adi F. / Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. In: Cancer Research. 1997 ; Vol. 57, No. 12. pp. 2373-2377.
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abstract = "To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat amplification protocol assay (131 samples) or by a radioactive in situ hybridization method for expression of the RNA component of human telomerase (hTR; 74 samples). A subset of samples was assayed by both methods, and the correlation was excellent (3b of 36; 83{\%}). With the exception of a carcinoid tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to strongly positive for both hTR and telomerase activity, except for foci of keratinization in squamous cell carcinomas. Telomerase positivity, with weak enzyme activity and/or low hTR expression, was present in basal epithelial cells of large bronchi, both histologically normal (26{\%}) and hyperplastic (71{\%}), and in 23{\%} of peripheral lung samples (in epithelium of small bronchi and bronchiolus or lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia, and CIS) were associated with telomerase dysregulation. Dysregulation in preneoplasia was manifested in three ways: almost all such lesions expressed hTR, although enzyme activity levels were several-fold lower than in the corresponding invasive tumors; cells throughout these multilayered processes expressed hTR; and intense, focal up- regulation of hTR occurred in CIS foci in the vicinity of invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia (possible precursor lesions for peripheral adenocarcinomas) were negative. Our studies demonstrate that dysregulation of telomerase occurs early in the multistage pathogenesis of bronchogenic lung carcinomas and that intense focal localized hTR expression in CIS may indicate imminent invasion.",
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AU - Kaiser, Larry

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AU - Lam, Stephen

AU - Wistuba, Ignacio I.

AU - Milchgrub, Sara

AU - Srivastava, Sudhir

AU - Piatyszek, Mieczyslaw A.

AU - Shay, Jerry W.

AU - Gazdar, Adi F.

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N2 - To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquantitative PCR-based telomeric repeat amplification protocol assay (131 samples) or by a radioactive in situ hybridization method for expression of the RNA component of human telomerase (hTR; 74 samples). A subset of samples was assayed by both methods, and the correlation was excellent (3b of 36; 83%). With the exception of a carcinoid tumor and a necrotic squamous cell carcinoma, all tumor cells were moderate to strongly positive for both hTR and telomerase activity, except for foci of keratinization in squamous cell carcinomas. Telomerase positivity, with weak enzyme activity and/or low hTR expression, was present in basal epithelial cells of large bronchi, both histologically normal (26%) and hyperplastic (71%), and in 23% of peripheral lung samples (in epithelium of small bronchi and bronchiolus or lymphoid aggregates). More advanced epithelial changes (metaplasia, dysplasia, and CIS) were associated with telomerase dysregulation. Dysregulation in preneoplasia was manifested in three ways: almost all such lesions expressed hTR, although enzyme activity levels were several-fold lower than in the corresponding invasive tumors; cells throughout these multilayered processes expressed hTR; and intense, focal up- regulation of hTR occurred in CIS foci in the vicinity of invasive cancers. Alveolar cells and areas of atypical adenomatous hyperplasia (possible precursor lesions for peripheral adenocarcinomas) were negative. Our studies demonstrate that dysregulation of telomerase occurs early in the multistage pathogenesis of bronchogenic lung carcinomas and that intense focal localized hTR expression in CIS may indicate imminent invasion.

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