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Cancer Stem Cell and Embryonic Development-Associated Molecules Contribute to Prognostic Significance in Ovarian Cancer
  1. Gulperi Oktem, MD*,
  2. Muzaffer Sanci, MD,
  3. Ayhan Bilir, PhD,
  4. Yusuf Yildirim, MD,
  5. Sibel D. Kececi, MD,
  6. Sule Ayla, MD§ and
  7. Sevinc Inan, MD
  1. * Department of Histology and Embryology, Ege University School of Medicine;
  2. Department of Gynecologıc Oncology, Ege Gynecology and Maternity Training and Research Hospital Izmir;
  3. Department of Histology and Embryology, Istanbul University Medical Faculty, Capa;
  4. § Suleymaniye Gynecology and Maternity Training and Research Hospital, Istanbul; and
  5. Department of Histology and Embryology, Celal Bayar University School of Medicine, Manisa, Turkey.
  1. Address correspondence and reprint requests to Gulperi Oktem, MD, Ege University School of Medicine, Department of Histology and Embryology, TR-35100 Izmir, Turkey. E-mail: gulperi.oktem{at}ege.edu.tr.

Abstract

Objectives Embryonic molecules and cancer stem cell signaling resemble each other, and they organize cancer modality. We hypothesized that similar immunohistochemical expressions between tumor spheroids and patients’ samples compared with clinical relevance would give an important clue in patients’ prognosis.

Methods Immunohistochemical expression of c-kit, Notch1, Jagged1, and Delta1 in 50 cases of primary ovarian tumors (10 endometrioid, 10 serous, 10 mucinous adenocarcinoma, 10 borderline serous, and 10 borderline mucinous tumors) and MDAH-2774 spheroids were investigated. Results were compared in both spheroids and tumor samples with morphologic parameters (histological grade) and clinical data (age, stage, tumor size, and metastasis).

Results High c-kit and Notch1 immunoreactivity was shown in spheroids, but interestingly immunoreactivity of these molecules in tumor samples was different from patients’ clinicopathological characteristics. In serous carcinoma, metastasis correlated with Notch1 immunoexpression; in mucinous carcinoma, Jagged1 immunohistochemistry correlated with grade, stage, and metastasis of tumor; in borderline serous and mucinous tumors, Jagged1 correlated with high grade. Moreover, Jagged1 correlated with stage and Notch1 with size in borderline mucinous tumor. Endometrioid carcinoma statistics showed that there was a correlation between age and Notch1 expression.

Conclusion Notch1, Jagged1, and Delta1 expressions might be useful markers for clinical prognosis of ovarian carcinomas; and Notch pathway, one of the most intensively studied putative therapeutic targets, may be a useful marker for cancer. Consequently, Jagged1 could be a marker for tumor grades and Notch1 as a marker for metastases.

  • Ovarian cancer stem cell
  • Notch pathway
  • c-kit
  • Multicellular tumor spheroids

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Footnotes

  • The authors declare that there are no conflicts of interest.