p16 Deletion in sarcomatoid tumors of the lung and pleura

Our plain-English summary of p16 Deletion in sarcomatoid tumors of the lung and pleura, by N. Tochigi, R. Attanoos, L.R. Chirieac, et al (Archives of Pathology & Laboratory Medicine, 2013).

The study

• Authors: N. Tochigi, R. Attanoos, L.R. Chirieac, T.C. Allen, P.T. Cagle, S. Dacic
• Journal: Archives of Pathology & Laboratory Medicine
• Published: 2013;137(5):632-6
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Context: The diagnosis of sarcomatoid neoplasms of the lung and pleura can be challenging. Homozygous deletion of 9p21, the locus harboring the p16 gene, has been reported as the most common genetic alteration in malignant mesotheliomas that is of potential diagnostic and prognostic significance.

Objectives: To evaluate the frequency of 9p21 deletion by fluorescence in situ hybridization in the primary sarcomatoid neoplasms of the lung and pleura and to determine its potential diagnostic utility.

Design: Ninety-two sarcomatoid neoplasms of the lung and pleura (32 sarcomatoid mesotheliomas, 15 sarcomatoid carcinomas, 32 solitary fibrous tumors, and 13 high-grade sarcomas) were examined for 9p21 deletion by fluorescence in situ hybridization.

Results: Deletion of 9p21 was most frequently seen in malignant mesotheliomas (81%), followed by sarcomatoid carcinomas (53%), sarcomas (25%), and solitary fibrous tumors (12.5%). Malignant mesotheliomas showed mostly homozygous deletion, whereas sarcomatoid carcinomas showed either homozygous or hemizygous deletion. None of the sarcomas showed homozygous deletion. There was a trend toward more frequent occurrence of 9p21 deletion in recurrent solitary fibrous tumors, but this did not reach statistical difference.

Conclusions: Deletion of 9p21 is common in sarcomatoid tumors of the lung and pleura. Despite statistically significant differences in the frequency of 9p21 deletion, and because of the large overlap among the study groups, this genetic abnormality cannot be used as a reliable diagnostic tool in the assessment of sarcomatoid lesions of the lung and pleura. A potential use of p16 deletion in predicting the biology of solitary fibrous tumors should be further explored.

In plain English

This laboratory study by pathologists tested 92 sarcomatoid (spindle-cell) tumors of the lung and pleura, taken from the authors' consultation files, for loss (deletion) of a region of chromosome 9 called 9p21, which contains the p16 gene. The tumors were 32 pleural sarcomatoid malignant mesotheliomas, 15 sarcomatoid lung carcinomas, 32 solitary fibrous tumors of the pleura and 13 sarcomas. The deletion was found in 26 of 32 mesotheliomas (81%), 8 of 15 sarcomatoid carcinomas (53%), 3 of 12 sarcomas (25%) and 4 of 32 solitary fibrous tumors (12.5%). The frequency in mesotheliomas differed significantly from that in carcinomas and from that in sarcomas. Among solitary fibrous tumors, 3 of 12 malignant tumors and 1 of 20 benign tumors had the deletion. That difference was not statistically significant. The authors concluded that, because the tumor groups overlapped, the deletion cannot be used as a diagnostic aid for these tumors. They said larger studies are needed on solitary fibrous tumors. The study did not examine asbestos exposure. The article gives 13 sarcomas in its methods but 12 in its results.

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 archived tumor tissue, tested for 9p21 (p16) deletion by fluorescence in situ hybridization (FISH)
• Who was studied: 92 sarcomatoid tumors of the lung and pleura from the authors' consultation files: 32 pleural sarcomatoid malignant mesotheliomas, 15 sarcomatoid lung carcinomas, 32 solitary fibrous tumors of the pleura (20 benign, 12 malignant) and 13 sarcomas of the lung and pleura (3 synovial sarcomas, 1 sarcoma of the pulmonary artery, 9 sarcomas not otherwise specified). No dates or patient details are given.
• Exposure: No asbestos or other exposure was studied. The study measured a genetic change (p16/9p21 deletion) in tumor tissue.
• Main results:
  • Sarcomatoid mesotheliomas: 26 of 32 (81%) had the deletion. No case had hemizygous (one-copy) loss alone.
  • Sarcomatoid lung carcinomas: 8 of 15 (53%) had the deletion. Homozygous (both-copy) deletion was seen in 6 of 8 and hemizygous-only loss in 2 of 8.
  • Sarcomas: 3 of 12 (25%) had the deletion. None of the synovial sarcomas had it.
  • Deletion frequency differed significantly between sarcomatoid mesothelioma and sarcomatoid carcinoma, and between sarcomatoid mesothelioma and sarcoma (P less than .001 for each). It did not differ significantly between sarcomatoid carcinoma and sarcoma.
  • Solitary fibrous tumors: 4 of 32 (12.5%) had the deletion. This was 3 of 12 malignant tumors (25%) versus 1 of 20 benign tumors (5%), a difference that was not statistically significant (P = .11).
• The authors' conclusion: The authors concluded that the deletion is common in sarcomatoid mesotheliomas. Because the different tumor groups overlapped, p16 deletion alone cannot be used as a diagnostic aid for sarcomatoid tumors of the lung and pleura.
• Limitations the authors state:
  • Only a small number of sarcomas showed the deletion, so the authors said these results should be interpreted with caution.
  • The study had few synovial sarcomas and used a higher FISH cutoff than an earlier study, which the authors said likely explains the different findings.
  • The sarcomas were high-grade tumors that were hard to subclassify precisely.
  • Larger series are needed to explore whether the deletion predicts aggressive solitary fibrous tumors.

Topics

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

Medical terms in this study, explained in our Lexicon: Sarcomatoid, Pleura, Neoplasm, Homozygous Deletion, Mesothelioma, Fluorescence In Situ Hybridization (FISH), Carcinoma, Solitary Fibrous Tumor.

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• Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis — D. Wu, K. Hiroshima, et al. (2013)
• The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: evidence-based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center — A.M. Marchevsky, N. LeStang, et al. (2017)
• Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma — Q. Hu, S. Akatsuka, et al. (2010)

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