Molecular characteristics of endometrial cancer coexisting with peritoneal malignant mesothelioma in Li-Fraumeni-like syndrome

Our plain-English summary of Molecular characteristics of endometrial cancer coexisting with peritoneal malignant mesothelioma in Li-Fraumeni-like syndrome, by A. Chao, C.H. Lai, Y.S. Lee, et al (BMC Cancer, 2015).

The study

• Authors: A. Chao, C.H. Lai, Y.S. Lee, S.H. Ueng, C.Y. Lin, T.H. Wang
• Journal: BMC Cancer
• Published: 2015;15:8
• Type of article: Case report
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Endometrial cancer that occurs concurrently with peritoneal malignant mesothelioma (PMM) is difficult to diagnose preoperatively.

Case Presentation: A postmenopausal woman had endometrial cancer extending to the cervix, vagina and pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy. Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications and some deletions were found in the endometrial cancer. The patient has been stable for 24 months after therapy. One of her four children was also found to carry the germline TP53 mutation.

Conclusions: Molecular characterization of the coexistent tumors not only helps us make the definite diagnosis, but also provides information to select targeted therapies if needed in the future. Identification of germline TP53 mutation further urged us to monitor future development of malignancies in this patient and encourage cancer screening in her family.

In plain English

This case report described one 54-year-old postmenopausal woman who had two separate cancers: endometrial cancer (in the lining of the uterus) and peritoneal malignant mesothelioma (in the lining of the abdomen). The article states she had no known asbestos exposure. The endometrial cancer was stage IIIc, grade 3. The mesothelioma had spread to both ovaries and several abdominal sites, and tissue staining supported its diagnosis. After chemotherapy with cisplatin and pemetrexed plus radiation, she remained clinically stable for 24 months, though scans still showed lesions that had not changed. Testing of tumor tissue and blood found a germline (inherited) TP53 mutation (Pro72Arg), which the authors described as compatible with Li-Fraumeni-like syndrome. The endometrial cancer also had a PIK3CA mutation and many large genetic changes. The mesothelioma had GNA11 and JAK3 mutations and few such changes. Three of her four children were tested: one son carried the TP53 mutation and two daughters did not. The authors concluded that molecular testing helped make the diagnosis and could guide future targeted treatment, and that family members should be enrolled in cancer screening.

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: case report (single patient, with genetic testing of three of her children)
• Who was studied: One 54-year-old postmenopausal woman (gravida 5, para 4) with abnormal bleeding. The authors are based at Chang Gung Memorial Hospital, Taiwan. Dates of care are not given.
• Exposure: No known asbestos exposure. The study looked at genetic changes in the tumors and blood, including a germline TP53 mutation.
• Main results:
  • Final diagnosis of the uterine tumor was endometrioid adenocarcinoma with cervical extension, positive vaginal margin and pelvic lymph node spread, FIGO stage IIIc, grade 3.
  • A coexisting mesothelioma (T2N0M0) was found extending to both ovaries, peritoneum, omentum, mesentery, cul-de-sac and bladder serosa.
  • Immunostaining of the peritoneal tumor (calretinin and CK5/6 positive; ER, PR and Ber-EP4 negative) supported a diagnosis of mesothelioma.
  • Treatment was cisplatin and pemetrexed (spelled 'premetrexed' in the article) every 3 weeks for 6 cycles, plus radiation to the pelvis and to the hepato-renal region.
  • The patient remained clinically stable for 24 months, although follow-up CT showed stationary lesions at Morrison's pouch.
  • A TP53 mutation (Pro72Arg) was found in the patient's blood and in both tumors, and was confirmed by Sanger sequencing.
  • The endometrial cancer had a somatic PIK3CA mutation (c.1624 G > A p.E542K), detected by both testing methods.
  • The mesothelioma had a GNA11 mutation.
  • The mesothelioma also had a JAK3 mutation (703C > T), listed in Table 1.
  • The endometrial cancer showed large regions of amplification, some deletions and loss of heterozygosity. The mesothelioma showed only a small number of copy number changes (amplification in 16p11.2 and loss of heterozygosity in 3p21.31 to 3p21.1).
  • Of the four children, three were tested. One son carried the TP53 germline mutation and two daughters were negative.
• The authors' conclusion: The authors concluded that molecular characterization of the coexisting tumors helped make a definitive diagnosis and may help in choosing targeted therapies in the future. They also stated that in Li-Fraumeni-like syndrome, family members should be enrolled in cancer screening.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Bilateral, Chemotherapy, Somatic Mutation.

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