Immunolocalization of integrins in the normal lung and in pulmonary carcinomas

Our plain-English summary of Immunolocalization of integrins in the normal lung and in pulmonary carcinomas, by G.K. Koukoulis, W.H. Warren, I. Virtanen, et al (Human Pathology, 1997).

The study

• Authors: G.K. Koukoulis, W.H. Warren, I. Virtanen, V.E. Gould
• Journal: Human Pathology
• Published: 1997;28(9):1018-25
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cryosections of normal adult lung (n = 7) and pulmonary epithelial tumors, including squamous (n = 8), adeno (n = 8), bronchioloalveolar (n = 5), and large cell (n = 4) carcinomas (SCC, ACC, BAC, LCC), carcinoids (Cd, n = 7), and neuroendocrine carcinomas (NEC) of variable grades (n = 14) were immunostained by the avidin-biotin peroxidase (ABC) method with monoclonal antibodies to the alpha1-6 and alpha(v) and the beta1-4 integrin subunits. Normal adult alveolar septae showed variably intense immunoreactivity for alpha1,3,6 and beta1, whereas reactions for alpha5 and alpha(v) were weaker and uneven; the remaining integrin subunits were not detected. Bronchial and bronchiolar epithelium showed variably intense staining for alpha2.3,6,v and beta1,4. Reactions were often, though not invariably, basally polarized. SCC, ADC, and LCC showed variably intense reactions for alpha2.3,6,v and beta1,4. BAC were strongly and uniformly stained for alpha1.3 and beta1. In Cd, alpha1,2,3,v and beta1 reactions were noted, whereas in NEC, weak alpha1,3 and beta1 staining was detected with only traces of alpha6 and alpha(v). We conclude that alveolar epithelial cells do not express the hemidesmosome-associated, laminin-binding integrin alpha6beta4 of the bronchial epithelium but rather the alpha1beta1 and alpha3beta1, collagen IV, and laminin receptors, respectively. SCC, ADC, and sampled LCC express an integrin repertory qualitatively similar to that of the bronchial epithelium. Distinct from the latter, the integrin repertory of BAC parallels that of the alveolar epithelium by its strong expression of the multipotential alpha1beta1 and alpha3beta1 integrins. NEC tumors do not display the laminin receptors alpha6beta4 and alpha6beta1 shown by SCC and ADC but express instead alpha1beta1, a collagen IV-laminin receptor rarely found in epithelial neoplasms except for BAC. In NEC tumors, integrins, especially alpha2, decrease with dedifferentiation. Notably distinct from epithelial mesotheliomas, the major fibronectin-binding integrin alpha5beta1 was not found in any type of lung carcinoma.

In plain English

This laboratory study examined integrins (proteins helping cells attach to surrounding tissue) in frozen normal adult lung and lung tumor samples from a Chicago hospital. It did not study asbestos exposure. Normal alveolar (air-sac) walls stained for alpha-1, alpha-3 and beta-1; their alpha-6 staining was seen in capillaries, not air-sac lining cells, and beta-4 was mostly absent. The bronchial lining stained for alpha-2, alpha-3 and beta-4, among others. Squamous cell carcinomas, adenocarcinomas and large cell carcinomas resembled the bronchial lining. Bronchioloalveolar carcinomas resembled the alveolar lining, with strong alpha-1 and alpha-3 staining. Carcinoids and neuroendocrine carcinomas differed from both; neuroendocrine carcinoma cells generally stained weakly and unevenly. No carcinoma type showed alpha-5 or alpha-4, the alpha subunits of two major fibronectin receptors; beta-1 was detected. The authors suggested lacking alpha-5 beta-1 may help distinguish lung adenocarcinomas from epithelial-type pleural mesotheliomas, which an earlier study reported consistently express it. They noted staining in thin alveolar walls was sometimes hard to resolve. Not detecting beta-2 in neuroendocrine tumor cells, unlike another study's cell cultures, might reflect lower method sensitivity or lymphoid cells in those cultures, they said.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory immunohistochemistry study of frozen surgical and autopsy lung tissue, stained by the avidin-biotin-peroxidase method with monoclonal antibodies to integrin subunits
• Who was studied: Tissue samples from Rush-Presbyterian-St Luke's Medical Center, Chicago. Methods section counts: normal adult lung (7, from autopsies or surgical specimens without cancer), squamous cell carcinoma (9), adenocarcinoma (10), bronchioloalveolar carcinoma (7), large cell carcinoma (8), carcinoid (8) and neuroendocrine carcinoma (18: 4 well-differentiated, 2 intermediate cell, 12 small cell). Dates of collection not given.
• Exposure: None. The study did not examine asbestos or any other exposure. It measured integrin staining in tissue.
• Main results:
  • Normal alveolar walls: alpha-1, alpha-3 and beta-1 staining was strong and extensive and involved all cell types of the walls. Beta-4 staining was mostly absent.
  • Normal alveolar walls: in the figure stained for alpha-6, staining was seen in the lining of collapsed capillaries and at the base of bronchiolar lining cells. The cells lining the air sacs were negative.
  • Normal bronchial and bronchiolar lining: alpha-3 staining was particularly strong, in a mosaic pattern along cell borders. Moderate alpha-2 staining was also seen, and alpha-6, alpha-v, beta-1 and beta-4 staining appeared at the base of the cells.
  • Squamous cell carcinomas: beta-4 staining was strong and extensive but confined to the border between tumor and surrounding tissue.
  • Adenocarcinomas: beta-4 staining was weaker and less extensive than in squamous cell carcinomas.
  • Bronchioloalveolar carcinomas: strong alpha-1 and alpha-3 staining was consistently seen, a pattern the authors found similar to normal alveolar lining.
  • Large cell carcinomas: strong alpha-3 staining outlined tumor cell borders in a mosaic pattern.
  • Neuroendocrine carcinomas, all variants: tumor cells showed weak and uneven staining for alpha-1, alpha-3 and beta-1. Some figures show stronger staining: strong but uneven staining in a well-differentiated neuroendocrine carcinoma, and moderate staining of some cells in a small cell neuroendocrine carcinoma.
  • Neuroendocrine carcinomas: no alpha-2 staining was seen, and beta-2 staining was limited to lymphoid cells, not tumor cells.
  • All types of lung carcinoma lacked the alpha subunits (alpha-5 and alpha-4) of two major fibronectin receptors, alpha-5 beta-1 and alpha-4 beta-1. The beta-1 subunit was detected in the tumors.
  • Two other integrins to which fibronectin-receptor activity has been attributed, alpha-3 beta-1 and alpha-v beta-1, were seen in the lung tumors.
• The authors' conclusion: The authors concluded that integrin patterns in lung tumors parallel those of their presumed normal counterpart cells. They suggested the findings may help separate bronchioloalveolar carcinoma from adenocarcinoma. They also suggested that the absence of the alpha-5 beta-1 fibronectin receptor may help separate lung adenocarcinomas from epithelial-type pleural mesotheliomas, which their earlier work had reported consistently express that receptor.
• Limitations the authors state:
  • Telling apart staining of different cell types in the thin alveolar walls was sometimes difficult.
  • Necrosis (dead tissue) was often extensive in intermediate and small cell neuroendocrine carcinomas.
  • The authors did not detect beta-2 in neuroendocrine tumor cells, although another study had reported low levels in neuroendocrine cell cultures using flow cytometry. They said this may reflect lower sensitivity of their own method.
  • As an alternative explanation for that difference, the authors said contamination of the other study's cell cultures by lymphoid cells could not be excluded.
  • The suggested fibronectin-receptor role of alpha-3 beta-1 and alpha-v beta-1 has not been proved by direct experiments.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Carcinoma, Monoclonal, Epithelium, Collagen, Neoplasm, Mesothelioma.

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• Findings from high resolution computed tomography of the lung and pleura of symptom free workers exposed to amosite who had normal chest radiographs and pulmonary function tests — S. Neri, A. Antonelli, et al. (1994)

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