CC BY-NC-ND 4.0 · J Lab Physicians 2021; 13(01): 050-057
DOI: 10.1055/s-0041-1724235
Original article

A Study of CD44 Positive Cancer Cells in Epithelial Ovarian Cancer and their Correlation with P53 And Ki67

Ketaki Kar
1   Department of Pathology, Midnapore Medical College & Hospital, Midnapore, West Bengal, India
,
Suman Ghosh
2   Department of Pathology, Nil Ratan Sircar Medical College & Hospital, Kolkata, West Bengal, India
,
Anup Kumar Roy
2   Department of Pathology, Nil Ratan Sircar Medical College & Hospital, Kolkata, West Bengal, India
› Author Affiliations

Abstract

Context  Epithelial ovarian carcinomas are one of the most common lethal gynecological malignancies. There is no specific symptom or biomarker for detection of this malignancy in early stage. So, the advanced stage, nature of frequent recurrences, and resistance to chemotherapies make it very difficult to deliver proper treatment to patients. Efforts are on to identify the presence of cancer stem cell by using a specific biomarker in epithelial ovarian cancer in the early stage.

Objectives  This study aims to identify the CD44 positive cancer cells in epithelial ovarian carcinoma of different histopathological types. It also intends to correlate the expression of CD44 with the expression of p53 and Ki67.

Materials and Methods Sections from diagnosed specimens of ovarian epithelial neoplasm had been fixed in 10% formalin and embedded in paraffin, and they were used for immunohistochemical (IHC) staining for CD44, p53, and Ki67, using a peroxidase kit with mouse monoclonal antibodies. Then, the slides were evaluated for both tumor cell percentage and intensity of immunoreactivity.

Statistical Analysis Chi-square had been used to find the significance of study. Significance level was considered at p value < 0.05

Results  In this study, 40 patients were included in a period of one and a half years. The present study suggested that the levels of CD44 expression were increased in epithelial ovarian cancer compared to borderline tumor. CD44 was positively correlated with the ki67 expression and tumor grade. High-grade serous, mucinous, and endometrioid tumors were associated with high CD44 expression. Positivity of CD44 was found significantly higher in case of positive status of p53 (z = 3.65; p < 0.0001).

Conclusion We can correlate CD44 positive cancer stem cells with grade of ovarian carcinomas, but for prognostic significance and therapeutic applications, more corroborative and multicentric works in this field are needed. CD44 can be targeted for therapy in recurrent and resistant cases of ovarian cancer.



Publication History

Article published online:
22 February 2021

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  • References

  • 1 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127 (12) 2893-2917
  • 2 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (06) 394-424
  • 3 Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 2010; 46 (04) 765-781
  • 4 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, et al. A. SEER Cancer Statistics Review, 1975–2012. Bethesda MD: National Cancer Institute; based on November 2014 SEER data submission, posted to the SEER web site, April 2015. Available at: https://seer.cancer.gov/archive/csr/1975_2012/, April 2015. Accessed March 10, 2019
  • 5 Chen VW, Ruiz B, Killeen JL, Coté TR, Wu XC, Correa CN. Pathology and classification of ovarian tumors. Cancer 2003; 97 (10) , Suppl) 2631-2642
  • 6 McCluggage WG. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology 2011; 43 (05) 420-432
  • 7 Mor G, Alvero A. The duplicitous origin of ovarian cancer. Rambam Maimonides Med J 2013; 4 (01) e0006
  • 8 El Hafez AA. Stemness markers in ovarian cancer: nature and implications. J Cytol Histol 2014; 5 (03) 1-2
  • 9 Ponta H, Sherman L, Herrlich PA. CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003; 4 (01) 33-45
  • 10 Bartakova A, Michalova K, Presl J, Vlasak P, Kostun J, Bouda J. CD44 as a cancer stem cell marker and its prognostic value in patients with ovarian carcinoma. J Obstet Gynaecol 2018; 38 (01) 110-114
  • 11 Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol 2000; 182 (03) 311-322
  • 12 Goh AM, Coffill CR, Lane DP. The role of mutant p53 in human cancer. J Pathol 2011; 223 (02) 116-126
  • 13 Ween MP, Oehler MK, Ricciardelli C. Role of versican, hyaluronan and CD44 in ovarian cancer metastasis. Int J Mol Sci 2011; 12 (02) 1009-1029
  • 14 McCluggage WG, Judge MJ, Clarke BA. et al; International Collaboration on Cancer Reporting. Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Mod Pathol 2015; 28 (08) 1101-1122
  • 15 Boger-Megiddo I, Weiss NS. Histologic subtypes and laterality of primary epithelial ovarian tumors. Gynecol Oncol 2005; 97 (01) 80-83
  • 16 Ross JS, Sheehan CE, Williams SS, Malfetano JH, Szyfelbein WM, Kallakury BV. Decreased CD44 standard form expression correlates with prognostic variables in ovarian carcinomas. Am J Clin Pathol 2001; 116 (01) 122-128
  • 17 Garzetti GG, Ciavattini A, Goteri G. et al. Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: index of proliferative activity with prognostic significance. Gynecol Oncol 1995; 56 (02) 169-174
  • 18 Zagorianakou N, Stefanou D, Makrydimas G. et al. CD44s expression, in benign, borderline and malignant tumors of ovarian surface epithelium. Correlation with p53, steroid receptor status, proliferative indices (PCNA, MIB1) and survival. Anticancer Res 2004; 24 (3a) 1665-1670
  • 19 Mondal SK, Banyopadhyay R, Nag DR, Roychowdhury S, Mondal PK, Sinha SK. Histologic pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms: a 10-year study in a tertiary hospital of eastern India. J Cancer Res Ther 2011; 7 (04) 433-437
  • 20 Agrawal P, Kulkarni DG, Chakrabarti PR, Chourasia S, Dixit M, Gupta K. Clinicopathological spectrum of ovarian tumors: A 5-year experience in a tertiary health care center. J Basic Clin Reprod Sci 2015; 4: 90-96
  • 21 Malik IA. A prospective study of clinico-pathological features of epithelial ovarian cancer in Pakistan. J Pak Med Assoc 2002; 52 (04) 155-158
  • 22 Bhattacharya M, Shinde SD, Purandare VN. A clinicopathological analysis of 270 ovarian tumours. J Postgrad Med 1980; 26 (02) 103-107
  • 23 Jha R, Karki S. Histological pattern of ovarian tumors and their age distribution. Nepal Med Coll J 2008; 10 (02) 81-85
  • 24 Maheshwari V, Tyagi SP, Saxena K. et al. Surface epithelial tumours of the ovary. Indian J Pathol Microbiol 1994; 37 (01) 75-85
  • 25 Siddiqui RB, Shankar BH, Khan IM. Morphological Patterns of Ovarian Neoplasms in Different Age Groups-A Center based study. PJMHS 2015; 9: 1139
  • 26 Janaki M, Kumar MP, Arora VS, Harish V, Lavanya A. Histopathological examination of primary ovarian tumors. Int J Res Health Sci 2015; 3: 217-249
  • 27 Ramachandran G, Harilal KR, Chinnamma KK, Thangavelu H. Ovarian neoplasms-a study of 903 cases. J. Obstet. And Gynec. 1972; 22: 309-315
  • 28 Hart WR. Borderline epithelial tumors of the ovary. Mod Pathol 2005; 18 (Suppl. 02) S33-S50
  • 29 Pelupessy NU, Andrijono A, Sutrisna B. et al. CD133, CD44, and ALDH1A1 as cancer stem cell markers and prognostic factors in epithelial ovarian cancer. Med J Indones 2019; 28: 63-69
  • 30 Chen M, Jin Y, Bi Y, Li Y, Shan Y, Pan L. Prognostic significance of lymphovascular space invasion in epithelial ovarian cancer. J Cancer 2015; 6 (05) 412-419
  • 31 Qian X, Xi X, Jin Y. The grading of lymphovascular space invasion in epithelial ovarian carcinoma. Int J Gynecol Cancer 2010; 20 (05) 895-899
  • 32 Heintz AP, Odicino F, Maisonneuve P. et al. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95 (Suppl. 01) S161-S192
  • 33 Zheng J, Wang Y, Zhao L, Zhao S, Cui M. Overexpression of CD44 and EpCAM may be associated with the initiation and progression of epithelial ovarian cancer. Int J Clin Exp Pathol 2017; 10: 4780-4786
  • 34 Sillanpää S, Anttila MA, Voutilainen K. et al. CD44 expression indicates favorable prognosis in epithelial ovarian cancer. Clin Cancer Res 2003; 9 (14) 5318-5324
  • 35 Harlozińska A, Bar JK, Sedlaczek P, Gerber J. Expression of p53 protein and Ki-67 reactivity in ovarian neoplasms. Correlation with histopathology. Am J Clin Pathol 1996; 105 (03) 334-340
  • 36 Korkolopoulou P, Vassilopoulos I, Konstantinidou AE. et al. The combined evaluation of p27Kip1 and Ki-67 expression provides independent information on overall survival of ovarian carcinoma patients. Gynecol Oncol 2002; 85 (03) 404-414
  • 37 Sardar K, Singh J, Tirkey S. Ki67 immuno-expression in ovarian tumors. IOSR Journal of Dental and Medical Sciences 2018; 17: 34-37
  • 38 Sylvia MT, Kumar S, Dasari P. The expression of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2-neu, p53 and Ki-67 in epithelial ovarian tumors and its correlation with clinicopathologic variables. Indian J Pathol Microbiol 2012; 55 (01) 33-37