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. 2001 Mar;54(3):201–204. doi: 10.1136/jcp.54.3.201

Downregulation of transforming growth factor ß type II receptor in laryngeal carcinogenesis

A Franchi 1, O Gallo 1, I Sardi 1, M Santucci 1
PMCID: PMC1731366  PMID: 11253131

Abstract

Aims—To investigate whether anomalies of transforming growth factor ß type II receptor (TGF-ß RII) expression occur in the early stages of laryngeal carcinogenesis and to assess their importance in the development of laryngeal squamous cell carcinoma. TGF-ß RII status was examined in laryngeal premalignant lesions coupled with malignant evolution and compared with a control group of similar lesions without progression to cancer.

Methods—Immunohistochemical staining for TGF-ß RII was performed on 15 paraffin wax embedded biopsies from patients with precancerous laryngeal lesions who subsequently developed invasive squamous cell carcinoma of the larynx, and on 30 control biopsies from patients who did not develop cancer in a comparable follow up period. In addition, DNA extracted from 18 preneoplastic lesions and eight squamous cell carcinomas was amplified by the polymerase chain reaction at the poly A and the poly GT regions of the TGF-ß RII gene.

Results—In the group of lesions with progression to carcinoma, 11 of 15 cases showed loss (< 20% of epithelial cells) of TGF-ß RII immunoreactivity, whereas among non-evolved lesions only five of 30 had similar altered expression of the receptor (p < 0.001, two tailed Fisher's exact test). All squamous cell carcinomas showed a degree of receptor expression comparable with that of the corresponding preneoplastic lesion, with the exception of one case, in which loss of the receptor was evident only in invasive cancer. Mutation of the poly A sequence of the TGF-ß RII gene was identified in only one precancerous lesion and in the subsequent squamous cell carcinoma.

Conclusions—These findings indicate that the downregulation of TGF-ß RII is an early event in laryngeal carcinogenesis, which may result in the loss of TGF-ß mediated growth inhibition, thereby facilitating the progression of laryngeal precancerous lesions to squamous cell carcinoma.

Key Words: laryngeal cancer • transforming growth factor-ß type II receptor

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Figure 1 (A) Laryngeal mucous glands showing intense immunoreactivity for transforming growth factor ß (TGF-ß) receptor type II. (B) Moderate laryngeal dysplasia with diffuse distribution of TGF-ß receptor type II in the basal and superficial layers of the squamous epithelium. This patient was free of disease five years after this biopsy. (C) Mild laryngeal dysplasia with pronounced loss of TGF-ß receptor type II expression: immunoreactivity is limited to the basal layers of the squamous epithelium. This patient developed a squamous cell carcinoma of the larynx three years later.

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Figure 2 Microsatellite analysis of the transforming growth factor ß receptor type II (TGF-ß RII) poly A repeat sequence. Genomic DNA from normal tissue (N), laryngeal dysplasia (Dys), and metachronous squamous cell carcinoma (T) was amplified by PCR, subjected to electrophoresis, and visualised with the silver staining method. Mutant bands are present in laryngeal dysplasia and in the subsequent squamous cell carcinoma.

Selected References

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