Authors
1 Pathology Department, Medicine Faculty, Cairo University, Cairo, Egypt
2 Pathology Department, Medicine Faculty, Cairo University, Cairo, Egyp
Abstract
Aims: Supporting evidences have been proposed that tumor initiating cells or cancer stem cells (CSCs) are principally sharing into tumor progress and relapse. Aldehyde dehydrogenase 1A1 (ALDH1A1), a stem cell marker, has currently been implicated in multiple human malignancies including ovarian carcinomas. The aims of this study were to assess immunohistochemical (IHC) expression of ALDH1A1 in ovarian epithelial tumors, tracking stem cells during ovarian cancer development and its relation with the clinicopathological features of such tumors.
Materials and Methods: In this experimental study, 42 paraffin blocks of ovarian tumor cases were retrieved retrospectively from the department of pathology, faculty of medicine, Cairo University during January 2013 to January 2015. Ovarian tumor paraffin blocks included 14 benign cystadenomas 14 border line tumors and 14 carcinomas. IHC reactions were carried out by using ALDH1A1 monoclonal antibody. Cases were classified into two groups of low and high ALDH1A1 expression. The chi-squared test (χ2) was used and data analyzes by SPSS 22 software.
Findings: High ALDH1A1 expression was reported in 50.0% of benign cystadenomas, 50.0% of borderline tumors and 85.7% of ovarian carcinomas with significant positive association with ovarian carcinomas (p=0.025). In ovarian carcinomas, positive relationship was detected between high ALDHA1 expression and advancing tumor grades but it didn’t reach statistical significance (p=0.054), no any significant relations were detected between ALDH1A1 immunohistochemical expression and age of patients, the documented size, laterality, histologic types and FIGO stage in all tumors (p>0.05).
Conclusion: ALDH1A1 is a potential biomarker for detecting CSCs in ovarian carcinomas and a prognostic marker. Also, it may act as a target for future therapy.
Keywords
- Lyoke CA, Ugwu GO, Ezugwu EC, Onah N, Ugwu O, Okafor O. Incidence, pattern and management of ovarian cancer at a tertiary medical center in Enugu, South East Nigeria. Ann Med Health Sci Res. 2013;3(3):417-21. [DOI:10.4103/2141-9248.117947] [PMID]
- Holschneider CH, Berek JS. Ovarian cancer: Epidemiology, biology, and prognostic factors. Semin Surg Onco. 2000;19(1):3-10. https://doi.org/10.1002/1098-2388(200007/08)19:1<3::AID-SSU2>3.0.CO;2-S [DOI:10.1002/1098-2388(200007/08)19:13.0.CO;2-S]
- Ono K, Tanaka T, Tsunoda T, Kitahara O, Kihara C, Okamoto A, et al. Identification by cDNA microarray of genes involved in ovarian carcinogenesis. Cancer Res. 2000;60(18):5007-11.
- Landen CN Jr, Goodman B, Katre AA, Steg AD, NICK AM, Stone RL, et al. Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther. 2010;9(12):3186-99. [DOI:10.1158/1535-7163.MCT-10-0563] [PMID]
- Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is amarker for normal and malignant human colonic Stem Cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69(8):3382-9. [DOI:10.1158/0008-5472.CAN-08-4418] [PMID]
- Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X, et al. ALDH1 expression correlates with favorable prognosis in ovarian cancers. Mod Pathol. 2009;22(6):817-23. [DOI:10.1038/modpathol.2009.35] [PMID]
- Liu Y, Lv DL, Duan JJ, Xu SL, Zhang JF, Yang XJ, et al. ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: A systematic review and meta-analysis. BMC Cancer. 2014;14:444. [DOI:10.1186/1471-2407-14-444] [PMID]
- Deng S, Yang X, Lassus H, Liang S, Kaur S, Ye Q, et al. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One. 2010;5(4):e10277. [DOI:10.1371/journal.pone.0010277] [PMID]
- Wang YC, Yo YT, Lee HY et al. ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. Am J Pathol. 2012;180(3):1159-69. [DOI:10.1016/j.ajpath.2011.11.015] [PMID]
- International Agency for Research on Cancer. Pathology and genetics of tumours of the breast and female genital organs. Eble GN, Tavassoli FA, Devilee P, editors. Lyon: IARC Press; 2003. pp. 114-29.
- Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells--perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 2006;66(19):9339-44. [DOI:10.1158/0008-5472.CAN-06-3126] [PMID]
- Lawrenson K, Gayther SA. Ovarian cancer: A clinical challenge that needs some basic answers. PLoS Med. 2009;6(2):e25. [DOI:10.1371/journal.pmed.1000025] [PMID]
- Tothill IE. Biosensors for cancer markers diagnosis. Semin Cell Dev Biol. 2009;20(1):55-62. [DOI:10.1016/j.semcdb.2009.01.015] [PMID]
- Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, et al. Aldehyde dehydrogenase in combination with CD133 define angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res. 2011;71(11):3991-4001. [DOI:10.1158/0008-5472.CAN-10-3175] [PMID]
- Chene G, Ouellet V, Rahimi K, Barres V, Meunier L, De Ladurantaye M, et al. Expression of stem cell markers in preinvasive tubal lesions of ovarian carcinoma. BioMed Research Int. 2015;808531. [DOI:10.1155/2015/808531] [PMID]
- Penumatsa K, Edassery SL, Barua A, Bradaric MJ, Luborsky JL. Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors. J Ovarian Res. 2010;3:28. [DOI:10.1186/1757-2215-3-28] [PMID]
- Chui MH, Wang Y, Wu RC, Seidman J, Kurman RJ, Wang TL, et al. Loss of ALDH1A1 expression is an early event in the pathogenesis of ovarian high-grade serous carcinoma. Mod Pathol. 2015;28(3):437-45. [DOI:10.1038/modpathol.2014.89] [PMID]
- Liu P, Brown S, Goktug T, Channathodiyil P, Kannappan V, Hugnot JP, et al. Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. Br J of Cancer. 2012;107(9):1488-97. in ovarian cancer tissues and sphere cultures. BMC [DOI:10.1038/bjc.2012.442] [PMID]
- Saw YT, Yang J, Ng SK, Liu S, Singh S, Singh M, et al. Characterization of aldehyde dehydrogenase isozymes Cancer. 2012;12:329. [DOI:10.1186/1471-2407-12-329] [PMID]
)
