Transmembrane Phosphatase with TEnsin Homologue (TPTE) Expression in Epithelial Ovarian Cancer


  • CA Adepiti
  • K Odunsi Department Gynaecological Oncology, Roswell Park Cancer Centre, Buffalo NY. Current affiliation: University of Chicago Medicine Comprehensive Cancer Centre.



Antigen-specific Immunotherapy, 'Cancer Testis' Antigen, Epithelial Ovarian Cancer, ETPTE, NY-ESO-1


Background: TPTE is a ‘Cancer Testis’ antigen that could be a candidate for targeted immunotherapy of epithelial ovarian cancer.

Objective: To determine the prevalence of expression and the impact of TPTE on clinical and survival outcomes in epithelial ovarian cancer.

Methods: Relevant medical information of 173 ovarian cancer patients (including Fallopian and primary peritoneal) managed at a Cancer Centre were retrieved. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of TPTE in the tumours. TPTE expression was correlated with the clinicopathologic and survival outcomes of the patients.

Results: TPTE was expressed by 45.1% (78/173) of the tested tumours. There was no significant difference in age between TPTE-positive and negative women (p = 0.93). TPTE expression was not significantly associated with the stage of the disease (p = 1.00), grade of disease (p = 0.71) and histology of the tumour (p = 0.17). There was no significant association between TPTE expression and the ease of optimum debulking (44.5% vs 44.3%, p = 0.54). TPTE expression was also not associated with a better response to therapy (p = 0.05). However, it was associated with slightly longer but not statistically significant progression-free survival (27.5 vs 20.6-months, p = 0.14) and overall survival (49.2 vs 28.0 months, p = 0.11).

Conclusion: This study shows that TPTE is expressed at a moderate frequency in epithelial ovarian cancers, and its expression is associated with marginally better survival outcomes.


Siegel RL, Miller KD, Jemal A. Cancer Statistics. CA Cancer J Clin 2017; 67: 7-30.

Ozols RF, Bundy BN, Greer BE. Fowler JM, Clark-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected Stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 2003; 21: 3194-3200.

Reid MB, Permuth JB, Sellers AT. Epidemiology of ovarian cancer a review. Cancer Bio Med 2017; 14: 9-32.

Berek JS, Crum C, Friedlander M. Cancer of the ovary, fallopian tube, and the peritoneum. Int J Gynaecol Obstet 2012; 119: S118.

Almeida L, Sakabe NJ, deOliveira AR, Silva MCC, Mundstein AS, Cohen T, et al. CT database: a knowledge-based of high-throughput and curated data on cancer-testis antigens. Nucleic Acids Res 2009; 37: D816-D819.

Gure AO, Stockert E, Arden KC, Boyer AD, Viars CS, Scanlan MJ, et al. CT10: a new cancer-testis (CT) antigen homologous to CT7 and the MAGE family, identified by representational difference analysis. Int J Cancer 2000; 85: 965-971.<726::aid-ijc21>;2-f

Szender JB, Papanicolauet-Sengos A, Eng KH, Miliotto JA, Lugade AA, Gnjatic S, et al. NY-ESO-1 expression predicts an aggressive phenotype of ovarian cancer. Gynecol Oncol 2017; 145: 420-445.

Odunsi K, Jungbluth AA, Stockert E, Quian F, Gnjatic S, Tammela J, et al. NY-ESO-1and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer. Cancer Res 2003; 63: 6076-6083.

Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3, 4, 5-triphosphate. J Biol Chem 1998; 273: 13375-13378.

Wu Y, Dowbenko D, Pisabarro MT, Dillard-Telm L, Koeppen H, Lasky LA, et al. PTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase. J Biol Chem 2001; 276: 21745-21753.

Dong XY, Su YR, Quian XP, Yang XA, Pang XW, Wu HY, et al. Identification of two novel CT antigens and their capacity to elicit antibody response to hepatocellular carcinoma patients. Br J Cancer 2003; 89: 291-297.

Singh AP, Bafna S, Chaudhary K, Venkatraman G, Smith L, Eudy JD, et al. Genome-wide expression profiling reveals transcriptomic variations and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer. Cancer Lett 2008; 259: 28-38.

Chen H, Rossier C, Morris MA, Scott HS, Gos A, Bairoch A, et al. A testis-specific gene, TPTE, encodes a putative transmembrane tyrosine phosphatase and maps to the pericentromeric region of human chromosomes 21 and 13, and to chromosomes 15, 22 and Y. Hum Genet 1999; 105: 399-409.

Jager D, Jager E, Knut A. Immune responses to tumor antigens: implications for antigen specific immunotherapy of cancer. J Clin Pathol 2001; 54: 669-74.

Kirkin AF, Dzhandzhugazyan KN, Zeuthen J. Cancer/testis antigens: structural and immunobiological properties. Cancer Invest 2002; 20: 222-36.

Kuemmel A, Simon P, Breitkreuz A, Rohlig J, Luxemburger U, Elsaber A, et al. Humoral immune responses to lung cancer patients against the Transmembrane Phosphatase with TEnsin homologue (TPTE). Lung Cancer 2015; 90: 334-341.

Alberts DS, Liu PY, Hannigan EV, O’Toole R, Williams SD, Young JA, et al. Intra peritoneal cisplatin plus cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 1996; 335: 1950-1955.

Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006; 354: 34-43.

Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carlson LF, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 2001; 19: 1001-1007.

McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and Cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996; 334: 1-6.

Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-83.

Singhal PK, Qian F, Keitz B, Driscoll D, Skipper J, Simpson A, Old L, Lele S, Odunsi K. TPTE “Cancer/Testis” antigen is a candidate target for immunotherapy in epithelial ovarian carcinoma. J Clin Oncol 2005; 23: 2583.

Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Mizukami M, et al. Clinical significance of cancer/testis antigens expression in patients with non-small cell lung cancer. Lung Cancer 2010; 68: 105-110.

Jager E, Chen YT, Drijfhout JW, Karbach J, Ringhoffer M, Arand M, et al. Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA)-A2 binding peptide epitopes. J Exp Med 1998; 187: 265-270.

Zeng G, Wang X, Robbin PF, Rosenberg PF, Wang RF. CD4(+) T cell recognition of MHC class II-restricted epitope with NY-ESO-I presented by a prevalent HLA DP4 allele: association with NY-ESO-1 antibody production. Proc Natl Acad Sci USA 2001; 98: 3964-369.

Leutkens T, Kobold S, Cao Y, Ristic M, Schilling G, Tams S, et al. Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation. Cancer Immunother 2014; 63: 1151-1162.

Yuan J, Adamow M, Ginsberg BA, Rasalan TS, Ritter E, Gallardo HF, et al. Integrated NY-ESO-1 antibody and CD8 (+) T-cell response correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci USA 2011; 108: 16723-16728.





Original Research