Cyr61, a member of ccn (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family, predicts survival of patients with endometrial cancer of endometrioid subtype

Gynecol Oncol. 2009 Jan;112(1):229-34. doi: 10.1016/j.ygyno.2008.09.039. Epub 2008 Nov 12.


Objectives: It has been reported that expression of Cyr61 decreased in endometrial cancers and cancer cell lines compared with normal endometrium, and forced expression of Cyr61 could suppress the growth of human endometrial cancer cells. However, in another report, Cyr61 was immunostained in most of endometrial cancer tissues analyzed. Thus, the aim of this study was to examine the expression of Cyr61 in endometrial cancer and to correlate Cyr61 expression with cinicopathologic factors in a larger cohort.

Methods: We used immunohistochemistry and RT-PCR to examine the expression of Cyr61 in 92 endometrial carcinomas of endometrioid subtype. We correlated the expression of Cyr61 with various clinicopathologic factors in patients with endometrioid adenocarcinoma. Survival analyses were performed by the Kaplan Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis.

Results: Cyr61 expression was high in 21 of 92 cases of endometrioid adenocarcinoma (22.8%). High expression of Cyr61 was related to poor survival of patients with endometrioid adenocarcinoma. Multivariate analysis including Cyr61 expression revealed that Cyr61 expression and positive lymph node metastasis (LNM) were independent prognostic factors for survival. Survival of patients with endometrioid adenocarcinoma could be stratified into three groups by combination of Cyr61 expression and positive LNM with an estimated 5-year survival rate of 96.5% for no LNM irrespective of Cyr61 expression (group A), 85.7% for positive LNM with low/moderate expression of Cyr61 (group B), and 0% for positive LNM with high expression of Cyr61 (group C)(p=0.18 for group A vs group B, p=0.008 for group B vs group C, and p<0.0001 for group A vs group C).

Conclusions: Cyr61 is highly expressed in some endometrial cancer of endometrioid subtype. Cyr61 expression and positive LNM were independent prognostic factors for patients with endometrioid adenocarcinoma. Cyr61 might be a new molecular marker to predict the prognosis of patients with endometrioid adenocarcinoma.

MeSH terms

  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / pathology
  • Cysteine-Rich Protein 61 / biosynthesis*
  • Cysteine-Rich Protein 61 / genetics
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • CCN1 protein, human
  • Cysteine-Rich Protein 61
  • RNA, Messenger