PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors
- 384 Downloads
Clonal loss of PTEN expression occurs frequently in endometrial carcinoma and endometrial hyperplasia. Limited data from immunohistochemical studies suggest that PTEN-null appearing endometrial glands are detectable in women without pathologic abnormalities, but the relationship of PTEN expression to endometrial cancer risk factors has not been extensively explored. We evaluated relationships between endometrial cancer risk factors and loss of PTEN expression in a set of benign endometrial samples prospectively collected from women undergoing hysterectomy and in endometrial cancer tissues from a population-based case–control study.
We used a validated PTEN immunohistochemical assay to assess expression in epidemiological studies designed to assess benign endometrium [Benign Reproductive Tissue Evaluation Study (n = 73); Einstein Endometrium Study (n = 19)], and endometrial cancer [Polish Endometrial Cancer Study (n = 148)] tissues. Associations between endometrial cancer risk factors (collected via study-specific risk factor questionnaires) and PTEN expression in endometrial tissues were determined using Fisher’s exact tests.
PTEN loss was detected in 19 % of benign endometrial tissues versus 55 % in endometrial cancers. NSAID use was statistically significantly associated with PTEN loss in the benign endometrium (p = 0.02).
Our data demonstrate that PTEN loss is detectable in endometrial tissues that are benign and malignant, with substantially more frequent loss in endometrial cancer compared with benign endometrium. However, alterations in expression were unrelated to most risk factors in this analysis, except for the association with NSAID use, which may represent a chance finding or reverse causality among patients with endometriosis who may have PTEN pathway abnormalities in eutopic endometrium. Further evaluation of factors associated with PTEN loss and long-term follow-up of women with PTEN-null endometrial glands may be useful in understanding early events in endometrial carcinogenesis.
KeywordsPTEN Endometrial cancer Risk factors
The study was supported by the Intramural Research Program of the National Cancer Institute.
- 1.American Cancer Society (2015) Cancer Facts and Figures 2015. American Cancer Society, AtlantaGoogle Scholar
- 7.Wang H, Douglas W, Lia M, Edelmann W, Kucherlapati R, Podsypanina K, Parsons R, Ellenson LH (2002) DNA mismatch repair deficiency accelerates endometrial tumorigenesis in Pten heterozygous mice. Am J Pathol 160(4):1481–1486. doi: 10.1016/S0002-9440(10)62573-4 PubMedCentralCrossRefPubMedGoogle Scholar
- 11.Allison KH, Tenpenny E, Reed SD, Swisher EM, Garica RL (2008) Immunohistochemical markers in endometrial hyperplasia: is there a panel with promise? A review. Appl Immunohistochem Mol Morphol AIMM Off Pub Soc Appl Immunohistochem 16(4):329–343. doi: 10.1097/PAI.0b013e318159b88e CrossRefGoogle Scholar
- 12.Lacey JV Jr, Mutter GL, Ronnett BM, Ioffe OB, Duggan MA, Rush BB, Glass AG, Richesson DA, Chatterjee N, Langholz B, Sherman ME (2008) PTEN expression in endometrial biopsies as a marker of progression to endometrial carcinoma. Cancer Res 68(14):6014–6020. doi: 10.1158/0008-5472.CAN-08-1154 PubMedCentralCrossRefPubMedGoogle Scholar
- 14.Wentzensen N, Bakkum-Gamez JN, Killian JK, Sampson J, Guido R, Glass A, Adams L, Luhn P, Brinton LA, Rush B, d’Ambrosio L, Gunja M, Yang HP, Garcia-Closas M, Lacey JV Jr, Lissowska J, Podratz K, Meltzer P, Shridhar V, Sherman ME (2014) Discovery and validation of methylation markers for endometrial cancer. Int J Cancer J Int du Cancer 135(8):1860–1868. doi: 10.1002/ijc.28843 CrossRefGoogle Scholar
- 16.Lotan TL, Gurel B, Sutcliffe S, Esopi D, Liu W, Xu J, Hicks JL, Park BH, Humphreys E, Partin AW, Han M, Netto GJ, Isaacs WB, De Marzo AM (2011) PTEN protein loss by immunostaining: analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin Cancer Res Off J Am Assoc Cancer Res 17(20):6563–6573. doi: 10.1158/1078-0432.CCR-11-1244 CrossRefGoogle Scholar
- 18.Lee H, Choi HJ, Kang CS, Lee HJ, Lee WS, Park CS (2012) Expression of miRNAs and PTEN in endometrial specimens ranging from histologically normal to hyperplasia and endometrial adenocarcinoma. Modern Pathol Off J US Can Acad Pathol Inc 25(11):1508–1515. doi: 10.1038/modpathol.2012.111 Google Scholar
- 23.Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A, Ovarian Cancer Association C (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies. Lancet Oncol 13(4):385–394. doi: 10.1016/S1470-2045(11)70404-1 PubMedCentralCrossRefPubMedGoogle Scholar
- 24.Neill AS, Nagle CM, Protani MM, Obermair A, Spurdle AB, Webb PM, Australian National Endometrial Cancer Study G (2013) Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case–control study, systematic review and meta-analysis. Int J Cancer J Int du Cancer 132(5):1146–1155. doi: 10.1002/ijc.27717 CrossRefGoogle Scholar
- 26.Setiawan VW, Matsuno RK, Lurie G, Wilkens LR, Carney ME, Henderson BE, Kolonel LN, Goodman MT (2012) Use of nonsteroidal anti-inflammatory drugs and risk of ovarian and endometrial cancer: the Multiethnic Cohort. Cancer Epidemiol Biomark Prev Pub Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 21(9):1441–1449. doi: 10.1158/1055-9965.EPI-12-0390-T CrossRefGoogle Scholar