Prognostic Impact of the Cancer Stem Cell–Related Marker NANOG in Ovarian Serous Carcinoma

ObjectiveThe objectives of this study were to assess cancer stem cell–related marker NANOG expression in ovarian serous tumors and to evaluate its prognostic significance in relation to ovarian serous carcinoma.MethodsNANOG protein expression was immunohistochemically evaluated in the ovarian tissue microarrays of 20 patients with benign ovarian serous tumors, 30 patients with borderline ovarian serous tumors, and 109 patients with ovarian serous carcinomas, from which 106 were of high-grade and 3 of low-grade morphology Immunohistochemical reaction was scored according to signal intensity and the percentage of positive cells in tumor samples. Pursuant to our summation of signal intensity and positive cell occurrence, we divided our samples into 4 groups: NANOG-negative, NANOG–slightly positive, NANOG–moderately positive, and NANOG–strongly positive group. Complete clinical data were obtained for the ovarian serous carcinoma group, and correlation between clinical data and NANOG expression was analyzed.ResultsA specific brown nuclear, or cytoplasmic reaction, was considered a positive NANOG staining. In terms of the ovarian serous carcinoma group, 69.7% were NANOG positive, 22.9% slightly positive, 22.9% moderately positive, and 23.9% strongly positive. All NANOG-positive cases were of high-grade morphology. Benign and borderline tumors and low-grade serous carcinomas were NANOG negative. There was no significant correlation between NANOG expression and clinical parameters in terms of the ovarian serous carcinoma group.ConclusionsPositive NANOG expression is significantly associated with high-grade ovarian serous carcinoma and is absent in benign, borderline, and low-grade serous lesions. In our study, there was no correlation between NANOG expression and clinical parameters, including its use in the prognosis of ovarian serous carcinoma.

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Prognostic Impact of Cancer Stem Cell-Like Phenotypes in Pancreatic Ductal Adenocarcinoma

Journal of Clinical & Experimental Pathology ◽

10.4172/2161-0681.1000295 ◽

2016 ◽

Vol 06 (05) ◽

Author(s):

Jin XH ◽

Yamamoto K ◽

Abe S ◽

Onishi I ◽

Kirimura S

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Pancreatic Ductal Adenocarcinoma ◽

Ductal Adenocarcinoma ◽

Prognostic Impact

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Expression of the cancer stem cell marker SSEA1 is associated with poor survival in metastatic high-grade serous carcinoma

Virchows Archiv ◽

10.1007/s00428-020-02850-4 ◽

2020 ◽

Vol 477 (5) ◽

pp. 677-685

Author(s):

Ben Davidson ◽

Arild Holth ◽

Hiep Phuc Dong

Keyword(s):

Stem Cell ◽

Survival Analysis ◽

Cancer Stem Cell ◽

Ovarian Carcinoma ◽

Progression Free Survival ◽

Stem Cell Marker ◽

Serous Carcinoma ◽

High Grade ◽

Poor Survival ◽

Free Survival

Abstract The objective of the present study was to perform a quantitative analysis of cancer stem cell (CSC) marker expression in ovarian carcinoma effusions. The clinical role of SSEA1 in metastatic high-grade serous carcinoma (HGSC) was additionally analyzed. CD133, Nanog, SOX2, Oct3/4, SSEA1, and SSEA4 protein expressions were quantitatively analyzed using flow cytometry (FCM) in 24 effusions. SSEA1 expression by immunohistochemistry was analyzed in 384 HGSC effusions. Highly variable expression of CSC markers by FCM was observed, ranging from 0 to 78% of Ber-EP4-positive cells in the case of CD133, with the largest number of negative specimens seen for SSEA4. SSEA1 expression by immunohistochemistry was found in HGSC cells in 336/384 (89%) effusions, most commonly focally (< 5% of cells). SSEA1 was overexpressed in post-chemotherapy disease recurrence specimens compared with chemo-naïve HGSC effusions tapped at diagnosis (p = 0.029). In univariate survival analysis, higher SSEA1 expression was significantly associated with poor overall survival (p = 0.047) and progression-free survival (p = 0.018), though it failed to retain its prognostic role in Cox multivariate survival analysis in which it was analyzed with clinical parameters (p = 0.059 and p = 0.111 for overall and progression-free survival, respectively). In conclusion, CSC markers are variably expressed in ovarian carcinoma effusions. SSEA1 expression is associated with disease progression and poor survival in metastatic HGSC. Silencing this molecule may have therapeutic relevance in this cancer.

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Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer

British Journal of Cancer ◽

10.1038/sj.bjc.6605762 ◽

2010 ◽

Vol 103 (3) ◽

pp. 382-390 ◽

Cited By ~ 167

Author(s):

A Lugli ◽

G Iezzi ◽

I Hostettler ◽

M G Muraro ◽

V Mele ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Prognostic Impact ◽

Stem Cell Markers ◽

Cell Markers ◽

Cancer Stem Cell Markers

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Prognostic impact of the cancer stem cell related markers ALDH1 and EZH2 in triple negative and basal-like breast cancers

Pathology ◽

10.1097/pat.0b013e3283534bcb ◽

2012 ◽

Vol 44 (4) ◽

pp. 303-312 ◽

Cited By ~ 25

Author(s):

Marina De Brot ◽

Rafael M. Rocha ◽

Fernando A. Soares ◽

Helenice Gobbi

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Triple Negative ◽

Prognostic Impact ◽

Breast Cancers

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Cancer Stem Cell and Embryonic Development-Associated Molecules Contribute to Prognostic Significance in Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31823228b2 ◽

2012 ◽

Vol 22 (1) ◽

pp. 23-29 ◽

Cited By ~ 11

Author(s):

Gulperi Oktem ◽

Muzaffer Sanci ◽

Ayhan Bilir ◽

Yusuf Yildirim ◽

Sibel D. Kececi ◽

...

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Histological Grade ◽

Prognostic Significance ◽

Notch Pathway ◽

Mucinous Carcinoma ◽

Clinicopathological Characteristics ◽

Serous Carcinoma ◽

Ovarian Carcinomas ◽

Clinical Prognosis

ObjectivesEmbryonic 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.MethodsImmunohistochemical 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).ResultsHigh 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.ConclusionNotch1, 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.

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