Reduced Fhit protein expression in human malignant mesothelioma

Our plain-English summary of Reduced Fhit protein expression in human malignant mesothelioma, by L. Pylkkänen, H. Wolff, T. Stjernvall, et al (Virchows Archiv, 2004).

The study

• Authors: L. Pylkkänen, H. Wolff, T. Stjernvall, A. Knuuttila, S. Anttila, K. Husgafvel-Pursiainen
• Journal: Virchows Archiv
• Published: 2004;444(1):43-8
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Human malignant mesothelioma (MM) is an aggressive neoplasm related to occupational exposure to asbestos and characterised by a long latency time. Multiple chromosomal deletions and DNA losses have been revealed in MM by studies performed with karyotypic, comparative genomic hybridisation and loss of heterozygosity (LOH) analyses. Among frequently deleted chromosomal sites, LOH at chromosome 3p has been detected in MM, suggesting the presence of one or several tumour suppressor genes that have an important role in development of the disease. The FHIT (fragile histidine triad) tumour suppressor gene, located at 3p14.2, has been proposed to be a target to major human lung carcinogens, such as tobacco smoke and asbestos. Although many studies have indicated decreased Fhit protein expression in a variety of malignancies, there is no report of FHIT gene aberrations or Fhit protein abnormalities in MM. We examined expression of the Fhit protein and LOH at the FHIT gene in malignant mesothelioma. Altogether, 13 paraffin embedded MM tumours were analysed for Fhit protein expression, and 21 fresh tumours and 10 cell cultures for LOH at the FHIT gene with two intragenic microsatellite markers. All tumours showed less intense immunostaining than normal bronchial epithelium or mesothelium. Fhit expression was absent or reduced in 54% (7 of 13) of the tumours, with the weakest staining observed in poorly differentiated areas. Allele loss was seen in 3 of 10 (30%) of the MM cell lines, but only in 1 of the 21 fresh tumours studied, suggesting concealment of LOH by normal cells present in MM tumours. In conclusion, our present data indicate a frequent decrease of Fhit protein expression, thus supporting the significance of FHIT inactivation in development of MM.

In plain English

This laboratory study from Finland examined the FHIT tumour suppressor gene in malignant mesothelioma. The authors studied 26 cases. By work history and/or fibre analysis, 19 of 25 patients had been exposed to asbestos at work, 6 were non-exposed, and 1 lacked data. In 13 paraffin-embedded tumours, staining for the Fhit protein was weaker in every tumour than in normal bronchial lining and normal mesothelium. It was absent or reduced in 7 of 13 (54%), with the weakest staining in poorly differentiated areas. The authors defined allele loss as the absence or marked decrease of one of the patient's two versions of the gene region, measured at two markers inside the gene. They found it in 3 of 10 cell cultures (30%) and in 1 of 21 fresh tumours; Table 2 lists this as 1 of 20. The authors thought normal cells mixed into fresh tumours probably hid allele loss there. The article did not report staining results separately for exposed and non-exposed patients. The authors concluded that absent or markedly reduced Fhit expression was frequent in mesothelioma, but that FHIT inactivation may be a late event.

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 study of tumour tissue and cell cultures: immunohistochemical staining for Fhit protein and loss of heterozygosity (allele loss) analysis at the FHIT gene
• Who was studied: 26 malignant mesothelioma cases, with diagnosis confirmed by the Finnish National Mesothelioma Panel. 13 paraffin-embedded tumours were stained for Fhit protein. 21 fresh frozen tumours and 10 cell cultures were analysed for allele loss. Most patients were male, aged 39 to 79 where recorded.
• Exposure: Occupational asbestos exposure, judged from occupational history and/or fibre analysis of tumour tissue. 19 of 25 patients were classed as exposed at work, 6 as non-exposed, and data were missing for 1. Fibre types were not named.
• Main results:
  • In all tumours examined, Fhit protein expression was decreased compared with normal bronchial columnar epithelium and mesothelium.
  • Of the 13 stained tumours, 4 showed markedly reduced expression, 3 considerably reduced expression and 6 positive expression. This makes absent or reduced expression in 7 of 13 (54%).
  • Staining was uneven within tumours: stronger in well-differentiated areas and weaker in poorly differentiated areas.
  • Allele loss at the FHIT gene markers was found in 3 of 10 cell cultures (30%) and in 1 of 21 fresh tumour samples (5%). Table 2 lists the fresh-tumour result as 1 of 20 (5%).
• The authors' conclusion: The authors concluded that absent or markedly reduced Fhit expression was frequent in malignant mesothelioma. They added that the staining pattern suggests FHIT inactivation may be a late event.
• Limitations the authors state:
  • The low rate of allele loss in fresh tumour samples was most likely caused by normal cells in the specimens hiding the loss.
  • The FHIT gene may be inactivated by other mechanisms, such as methylation, that the allele loss analysis would not detect.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Neoplasm, Occupational Exposure, Latency, Epithelium, Mesothelium.

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