Molecular association of functioning stroma with carcinoma cells in the ovary: A preliminary study

Narikiyo,Mika; Yano,Mitsutake; Kamada,Kouichi; Katoh,Tomomi; Ito,Kozue; Shuto,Masayo; Kayano,Hidekazu; Yasuda,Masanori

doi:10.3892/ol.2019.9992

Molecular association of functioning stroma with carcinoma cells in the ovary: A preliminary study

Authors:
- Mika Narikiyo
- Mitsutake Yano
- Kouichi Kamada
- Tomomi Katoh
- Kozue Ito
- Masayo Shuto
- Hidekazu Kayano
- Masanori Yasuda
View Affiliations

Affiliations: School of Medical Technology, Faculty of Health and Medical Care, Saitama Medical University, Hidaka, Saitama 350‑1298, Japan, Department of Pathology, Saitama Medical University International Medical Center, Hidaka, Saitama 350‑1298, Japan
Published online on: January 30, 2019 https://doi.org/10.3892/ol.2019.9992
Pages: 3562-3568

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The cancer stroma serves an important role in tumour behaviours, including invasion, metastasis, and response to chemotherapy. The stroma of ovarian carcinoma is sometimes specialized, with luteinisation and/or hyperthecosis, and is designated as the ‘functioning stroma’ because it exerts endocrine function and produces sex steroid hormones. In the present study, 14 ovarian cancers with functioning stroma, comprising 7 endometrioid carcinomas and 7 clear cell carcinomas, were analysed to evaluate the molecular association of the functioning stroma with carcinoma cells. The median age of the patients was 67 years (range, 52‑85 years); 13 patients were postmenopausal, and one was in perimenopause. Serum oestrogen values ranged from 10 to 129 ng/ml, with a median of 51 ng/ml. Sequence abnormalities in AT‑rich interaction domain 1A (ARID1A), phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α (PIK3CA), Kirsten rat sarcoma viral proto‑oncogene (KRAS) and phosphatase and tensin homolog (PTEN) were examined in whole tumours. For cancers positive for sequence abnormalities, their localization in carcinoma cells and/or stromal cells was examined. A total of 8 mutations ‑ ARID1A (L2155L), PIK3CA (H1047R), KRAS (Q12V, E31K, Q61L), and PTEN (C105fs*8) ‑ were identified in the whole tumours of 5 patients. Seven of these eight mutations were detected only in carcinoma cells. However, one case of endometrioid carcinoma had a KRAS (E31K) mutation in both carcinoma and stromal cells. In conclusion, although functioning stromal cells of ovarian cancer are usually thought to be non‑neoplastic, some may share an origin with carcinoma cells.

View Figures

View References

1	Bhowmick NA and Moses HL: Tumor-stroma interactions. Curr Opin Genet Dev. 15:97–101. 2005. View Article : Google Scholar : PubMed/NCBI
2	Kim JB, Stein R and O'Hare MJ: Tumour-stromal interactions in breast cancer: The role of stroma in tumourigenesis. Tumour Biol. 26:173–185. 2005. View Article : Google Scholar : PubMed/NCBI
3	Tlsty TD and Coussens LM: Tumor stroma and regulation of cancer development. Annu Rev Pathol. 1:119–150. 2006. View Article : Google Scholar : PubMed/NCBI
4	Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD and Cunha GR: Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 59:5002–5011. 1999.PubMed/NCBI
5	Nagasaki T, Hara M, Nakanishi H, Takahashi H, Sato M and Takeyama H: Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: Anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer. 110:469–478. 2014. View Article : Google Scholar : PubMed/NCBI
6	Liu J, Chen S, Wang W, Ning BF, Chen F, Shen W, Ding J, Chen W, Xie WF and Zhang X: Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways. Cancer Lett. 379:49–59. 2016. View Article : Google Scholar : PubMed/NCBI
7	Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, et al: Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 487:500–504. 2012. View Article : Google Scholar : PubMed/NCBI
8	Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP and Eng C: Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. Nat Genet. 32:355–357. 2002. View Article : Google Scholar : PubMed/NCBI
9	Wernert N, Locherbach C, Wellmann A, Behrens P and Hügel A: Presence of genetic alterations in microdissected stroma of human colon and breast cancers. Anticancer Res. 21:2259–2264. 2001.PubMed/NCBI
10	Paterson RF, Ulbright TM, MacLennan GT, Zhang S, Pan CX, Sweeney CJ, Moore CR, Foster RS, Koch MO, Eble JN and Cheng L: Molecular genetic alterations in the laser-capture-microdissected stroma adjacent to bladder carcinoma. Cancer. 98:1830–1836. 2003. View Article : Google Scholar : PubMed/NCBI
11	Akahane T, Hirasawa A, Tsuda H, Kataoka F, Nishimura S, Tanaka H, Tominaga E, Nomura H, Chiyoda T, Iguchi Y, et al: The origin of stroma surrounding epithelial ovarian cancer cells. Int J Gynecol Pathol. 32:26–30. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tuhkanen H, Anttila M, Kosma VM, Heinonen S, Juhola M, Helisalmi S, Kataja V and Mannermaa A: Frequent gene dosage alterations in stromal cells of epithelial ovarian carcinomas. Int J Cancer. 119:1345–1353. 2006. View Article : Google Scholar : PubMed/NCBI
13	Permuth-Wey J and Sellers TA: Epidemiology of ovarian cancer. Methods Mol Biol. 472:413–437. 2009. View Article : Google Scholar : PubMed/NCBI
14	McConechy MK, Ding J, Senz J, Yang W, Melnyk N, Tone AA, Prentice LM, Wiegand KC, McAlpine JN, Shah SP, et al: Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Mod Pathol. 27:128–134. 2014. View Article : Google Scholar : PubMed/NCBI
15	Murakami R, Matsumura N, Brown JB, Higasa K, Tsutsumi T, Kamada M, Abou-Taleb H, Hosoe Y, Kitamura S, Yamaguchi K, et al: Exome sequencing landscape analysis in ovarian clear cell carcinoma shed light on key chromosomal regions and mutation gene networks. Am J Pathol. 187:2246–2258. 2017. View Article : Google Scholar : PubMed/NCBI
16	Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, Senz J, McConechy MK, Anglesio MS, Kalloger SE, et al: ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 363:1532–1543. 2010. View Article : Google Scholar : PubMed/NCBI
17	Kim SI, Lee JW, Lee M, Kim HS, Chung HH, Kim JW, Park NH, Song YS and Seo JS: Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing. Gynecol Oncol. 148:375–382. 2018. View Article : Google Scholar : PubMed/NCBI
18	Scully RE YR and Clement PB: Tumors with functioning stroma. Tumors of the ovary, maldeveloped gonads, fallopian tube and broad ligament. In: Atlas of Tumor Pathology Armed Forces Institute of Pathology; Washington, DC: pp. pp373–378. 1998
19	Kato N, Hayasaka T, Takeda J, Osakabe M and Kurachi H: Ovarian tumors with functioning stroma: A clinicopathologic study with special reference to serum estrogen level, stromal morphology and aromatase expression. Int J Gynecol Pathol. 32:556–561. 2013. View Article : Google Scholar : PubMed/NCBI
20	Katoh T, Yasuda M, Hasegawa K, Kozawa E, Maniwa J and Sasano H: Estrogen-producing endometrioid adenocarcinoma resembling sex cord-stromal tumor of the ovary: A review of four postmenopausal cases. Diagn Pathol. 7:1642012. View Article : Google Scholar : PubMed/NCBI
21	Stewart CJ, Leung Y, Walsh MD, Walters RJ, Young JP and Buchanan DD: KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: Association with concurrent endometriosis. Hum Pathol. 43:1177–1183. 2012. View Article : Google Scholar : PubMed/NCBI