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Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor.

Sato N, Takagi K, Suzuki T, Miki Y, Tanaka S, Nagase S, Warita H, Fukudo S, Sato F, Sasano H, Ito K - Int. J. Gynecol. Cancer (2014)

Bottom Line: Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2).Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival.Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.

View Article: PubMed Central - PubMed

Affiliation: Tohoku University Graduate School of Medicine, Sendai, Japan.

ABSTRACT

Objective: Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma.

Materials and methods: A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records.

Results: Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.

Conclusions: These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease.

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Disease-free (A, C, and E) and overall (B, D, and F) survival of the 87 patients with endometrial cancer according to CRH (A and B), CRHR1 (C and D), and CRHR2 (E and F) status determined by the Kaplan-Meier method. P values were evaluated using Cox model.
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Figure 2: Disease-free (A, C, and E) and overall (B, D, and F) survival of the 87 patients with endometrial cancer according to CRH (A and B), CRHR1 (C and D), and CRHR2 (E and F) status determined by the Kaplan-Meier method. P values were evaluated using Cox model.

Mentions: Corticotropin-releasing hormone status was not significantly associated with disease-free (P = 0.17, Fig. 2A) or overall (P = 0.23, Fig. 2B) survival in any of the patients. In contrast, CRHR1 status was significantly associated with an increased incidence of recurrence (P = 0.023, Fig. 2C) and worse prognosis (P = 0.009, Fig. 2D). Corticotropin-releasing hormone receptor 2 status was not significantly associated with the incidence of recurrence (P = 0.61, Fig. 2E) but was marginally associated with better clinical outcome (P = 0.093, Fig. 2F). Similar tendencies were also detected when the cases were classified into 3 groups according to immunointensity (ie, negative, weakly positive, and strongly positive22) (disease-free survival: P = 0.15 for CRH; P = 0.019 for CRHR1; and P = 0.76 for CRHR2) (Supplemental Digital Content Figure S1 [A–C], http://links.lww.com/IGC/A232) and overall survival (P = 0.010 for CRH; P = 0.003 for CRHR1; and P = 0.24 for CRHR2; data not shown).


Immunolocalization of corticotropin-releasing hormone (CRH) and its receptors (CRHR1 and CRHR2) in human endometrial carcinoma: CRHR1 as a potent prognostic factor.

Sato N, Takagi K, Suzuki T, Miki Y, Tanaka S, Nagase S, Warita H, Fukudo S, Sato F, Sasano H, Ito K - Int. J. Gynecol. Cancer (2014)

Disease-free (A, C, and E) and overall (B, D, and F) survival of the 87 patients with endometrial cancer according to CRH (A and B), CRHR1 (C and D), and CRHR2 (E and F) status determined by the Kaplan-Meier method. P values were evaluated using Cox model.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4215916&req=5

Figure 2: Disease-free (A, C, and E) and overall (B, D, and F) survival of the 87 patients with endometrial cancer according to CRH (A and B), CRHR1 (C and D), and CRHR2 (E and F) status determined by the Kaplan-Meier method. P values were evaluated using Cox model.
Mentions: Corticotropin-releasing hormone status was not significantly associated with disease-free (P = 0.17, Fig. 2A) or overall (P = 0.23, Fig. 2B) survival in any of the patients. In contrast, CRHR1 status was significantly associated with an increased incidence of recurrence (P = 0.023, Fig. 2C) and worse prognosis (P = 0.009, Fig. 2D). Corticotropin-releasing hormone receptor 2 status was not significantly associated with the incidence of recurrence (P = 0.61, Fig. 2E) but was marginally associated with better clinical outcome (P = 0.093, Fig. 2F). Similar tendencies were also detected when the cases were classified into 3 groups according to immunointensity (ie, negative, weakly positive, and strongly positive22) (disease-free survival: P = 0.15 for CRH; P = 0.019 for CRHR1; and P = 0.76 for CRHR2) (Supplemental Digital Content Figure S1 [A–C], http://links.lww.com/IGC/A232) and overall survival (P = 0.010 for CRH; P = 0.003 for CRHR1; and P = 0.24 for CRHR2; data not shown).

Bottom Line: Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2).Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival.Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.

View Article: PubMed Central - PubMed

Affiliation: Tohoku University Graduate School of Medicine, Sendai, Japan.

ABSTRACT

Objective: Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma.

Materials and methods: A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records.

Results: Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.

Conclusions: These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease.

Show MeSH
Related in: MedlinePlus