Expression Profile And Prognostic Role Of GR,ER And PR In Proximal And Distal Gastric Cancer

Background and Purpose Gastric cancer is the common malignant tumor in China. The proximal gastric cancer’s(PGC) incidence showed an upgrade trend in recent years. It is generally believed that the clinical biological behavior of PGC were different from the other parts of gastric cancers. It has been reported that the PGC have a worse prognosis than other parts. But the reason was not clear. The newly proved that the gastrin receptor(GR), estrogen receptor(ER)and progesterone receptor(PR) were expressed in gastric cancers and mucosa tissues. At present, the three kinds of receptors mainly studied in cancer cells or in tumors. However, the GR, ERand PR expression difference between the PGC and distal gastric cancers(DGC) were rare studied. This study was to detect the proteins of GR, ERα, ERβ, and PRand evaluate their clinicopathologic characteristics(age, gender, type, stage, lymph node metastasis, etc.) and prognosis in PGC and DGC. Also provide a reference for targeted and endocrine therapy.Methods Collected 15 case PGC patient tissues and 15 case DGC patient tissues samples.(With similar age, sex, pathological stage and type), and using immunohistochemical to detect the expression of GR, ERα, ERβ and PR in PGC and DGC tissues and adjacent normal mucosa tissues. The association between four receptors and the clinicopathological features was calculated by Chi-square test or Fisher’s exact test. The relationship between expression of three receptors and prognosis was analyzed by Kaplan-Meier method and the Cox proportional hazard regression model.Results1. The detect result show that such as GR, ERα, ERβ and PR were found in both gastric cancer tissues and adjacent non-cancerous tissues. The positive staining of GR was mainly in the cytoplasm. While the ERα, ERβ and PR both expressed in cell nucleus and cytoplasm.2.GR expressed in gastric cancer tissue were significantly higher than the adjacent normal mucosa tissues, while ERα, ERβ and PR were contrary. The difference were significant except ERβ(P<0.05).The positive rate of GR is 86.7% in proximal gastric cancer tissues which significant higher than the DGC tissues 40%(P<0.01). And the expression of GR was associated with gender, depth of invasion, Borrmann and Lauren types in the comparison of PGC and DGC(P<0.01). In contrast, there was no significant association with size, age and TNM stage(P>0.05). The positive rates of GR in proximal and distal gastric tumors were 88.9% and 33.3% at male patient(0.01<P<0.05). In addition to the expression of ERβ was associated with depth of invasion(P < 0.05), ERα, ERβand PR had no statistical association with all clinicopathologic characteristics in the comparison of proximal and distal gastric cancers(P>0.05). The metastasis rate of lymph nodes in proximal gastric cancers was 86.7% higher than the distal gastric cancer’s 53.3%. The difference were no significant(P>0.05).3. GR, ERα and PR expression positive rate were no significant difference with different gender, age, tumor size of all tumors(P>0.05), But associated with Borrmann types(P<0.05). The positive expression rate of ERβ associated with the TNM stage(P<0.05). At the Lauren types, all the 9 case of diffuse gastric cancer tissue were expressed GR which significant higher than the intestinal type and mixed type(P<0.05). ERα, ERβ and PR Expression positive ratein males are lower than females. The difference were no significant(P>0.05).With the increase of tumor stage and depth of invasion, the rate of ERα, ERβand PR expression positive were decline, while GR was increased. The difference were no significant too(P>0.05).4.With the univariate survival analysis, Kaplan–Meier survival curves demonstrated that distal gastric cancer patients had badprognosis than proximal gastric cancer patients(MST:41.0 months V.S 58.0 months, P =0.05). And GR-negative patients had better prognosis than GR-positive patients(MST:61.0months V.S 41.0 months, P = 0.028). Meanwhile, ERβ-positive patients also had better median survival time than ERβ-negative patients(MST:61.0 months V.S 42.0 months, P = 0.031).But the ERα and PR expression positive rate had no significant difference with clinic prognosis(P>0.05).Multiple survival analysis that Age and TNM stage were the independent prognostic factors for gastric cancerpatients, but GR, ERα, ERβ, and PR were not.Conclusions1.The detect result show that such as GR, ERα, ERβ and PR were found in both gastric cancer tissues and adjacent non-cancerous tissues.GR expressed in gastric cancer tissue were significantly higher than the adjacent normal mucosa tissues, while ERα, ERβ and PR were contrary.2.The positive rate of GR in PGCtissues significant higher than the DGC tissues. There were associated with gender, depth of invasion, Borrmann and Lauren types. While the expression of ERα, ERβand PR had no statistical association in the comparison of PGC and DGC.3.The positive rate of GR in PGCtissues significant higher than the DGC tissue. May affect their prognosis. But the ERα, ERβand PR were not.4.GR, ERβ and the tumor locationmay be as one of the comprehensive factors affected the gastric cancer prognosis. ERαand PR have a limited value in prognosis.