Elsevier

Human Pathology

Volume 32, Issue 3, March 2001, Pages 274-281
Human Pathology

Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas*,**

https://doi.org/10.1053/hupa.2001.22752Get rights and content

Abstract

Lung adenocarcinomas are heterogeneous clinically and histologically. Expression of the mucin genes was analyzed as a molecular marker of glandular cytodifferentiation in primary lung adenocarcinomas. Expression was correlated with histopathologic subtypes of World Health Organization classification with the aim of investigating the histogenesis of primary lung adenocarcinomas. Thirty-four primary lung adenocarcinomas were examined by in situ hybridization for mucin gene expression (MUC1-4, MUC5AC, MUC5B, MUC6-7) and by immunohistochemistry for MUC5AC and MUC5B apomucin expression. Mucinous bronchioloalveolar carcinoma (BAC) had a homogeneous pattern of mucin gene expression different from those of other types of lung adenocarcinoma, involving secreted mucins (MUC5AC, MUC5B, and MUC6) and membrane-bound mucins (MUC1, MUC3, and MUC4). Non-BAC adenocarcinoma and mucinous BAC aberrantly expressed mucin genes MUC3, and MUC3 and MUC6, respectively, which are undetectable in normal fetal and adult lung. Our results show the particular phenotype of mucin gene expression in mucinous type of BACs and the heterogeneous expression of respiratory and nonrespiratory mucins in the other types. This finding supports the theory of a common progenitor cell with the potential of multicellular differentiation. From a practical point of view, the aberrant expression of MUC3 and MUC6 could serve as a diagnostic marker in the management of the mucinous type of bronchioloalveolar carcinomas. HUM PATHOL 32:274-281. Copyright © 2001 by W.B. Saunders Company

Section snippets

Tissue selection and histologic definition

Surgical specimens of primary lung adenocarcinomas were collected from 34 patients (mean age 62 years; range 37-79 years). The patients had no metastases at the time of surgery and no pleural disease or other tumor at any site during the follow-up (at least 18 months of postoperative clinical follow-up available). Twenty-five of 34 patients had a smoking history. The pathology of the tumors was confirmed by the consensus of 2 pathologists. Of the 34 selected adenocarcinomas, 17 cases were

Histochemistry and cytokeratin expression

Mucus secretion was detected in all cases of mucinous-type BACs (Fig 1A), in 3 of 8 cases of nonmucinous-type adenocarcinomas in very limited areas, and in 12 of 17 cases of non-BACs.

. Mucinous-type BAC. (A) Well differentiated and mucus-secreting tumor cells are growing along the slightly thickened alveolar walls. (HES-astra blue; original magnification ×100.) (B) MUC5AC gene mRNAs by in situ hybridization. The signal is intense and diffuse in all carcinomatous cells (arrow). (Methyl green

Discussion

The present study assessed the pattern of mucin expression for MUC1-4, MUC5AC, MUC5B, and MUC6-7 at the mRNA level in 34 primary lung adenocarcinomas (17 BACs, 17 non-BACs) and for MUC5AC and MUC5B at the protein level in 25 cases. Lung adenocarcinomas are known to be very heterogeneous clinically and histologically. Mixtures of acinar, papillary, bronchioloalveolar, and solid adenocarcinoma with mucin formation are common. The definition of BACs is now restricted to noninvasive tumors without

Acknowledgements

The authors thank the members of European consortium (contract CEE BMH4-CT98-3222), especially Ingemar Carlstedt, for providing polyclonal antibodies against MUC5AC and MUC5B, and M. C. Dieu, E. Deschodt, V. Vervaecke, and V. Dumetz for excellent technical assistance.

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    *

    Supported by Association pour la Recherche sur le Cancer and CHU de Lille, contract grant number 96/09.29/95,95, and by the Ligue contre le Cancer du Pas de Calais.

    **

    Address correspondence and reprint requests to Marie-Christine Copin, MD, PhD, Service d'Anatomie et Cytologie Pathologiques, Hôpital Calmette, CHRU, Bd J. Leclercq, 59037 Lille Cedex, France.

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