The diagnosis and pathological value of combined detection of HE4 and CA125 for patients with ovarian cancer.

OBJECTIVE: To evaluate the value of individual and combined measurement of human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125) in the diagnosis of ovarian cancer. METHODS: A clinical case-control study was performed in which the levels of serum HE4 and CA-125 of subjects with malignant, borderline, benign ovarian tumors and healthy women were measured before surgery. An immunohistochemistry method was used to measure the expression of HE4 in different tissues. Statistical analysis was performed to determine the relationship between the level of HE4 and the pathologic type as well as the stage of the ovarian tumors. RESULTS: The level of HE4 in the serum was significantly elevated in the malignant ovarian cancer group compared with other groups. Women with benign ovarian tumors and non-neoplastic lesions, and healthy women were designated as references. When the level of HE4 in the serum was 58.66 pmol/L, the sensitivity and specificity of HE4 in diagnosing malignant ovarian tumors was 82.35% and 96.03%, respectively. The level of HE4 was negatively correlated with the differentiation extent of the tumors whereas positively correlated to the clinical staging. In the groups of malignant and borderline tumors, the levels of HE4 were higher than the other groups. The expression of HE4 was significant higher in the serous types of ovarian tumors than that of the mucous types (P<0.05). The level of HE4 in the serum and tissues were positively correlated with each other. CONCLUSION: HE4 can be used as a novel clinical biomarker for predicting malignant ovarian tumors and its expression was closely related with the clinical pathological features of malignant ovarian tumors.

[Relationship between expression of hyaluronan and pathologic features of ovarian adenocarcinoma].

BACKGROUND & OBJECTIVE: Hyaluronan (HA) is one of the major components of extra-cellular mesenchyma (ECM), which is secreted by several kinds of cells, including tumor cells. HA plays a role in cellular location and proliferation. It also takes part in the tumor cell motion and proliferation. It has been found that there was HA metabolism imbalance during the development of the solid tumors, and that, HA and its ligands might be related to tumor invasion, metastasis, and prognosis. The purpose of our research was to investigate the relationship among HA, the major ligand of cell adhesive molecule CD44, and pathologic types of ovarian adenocarcinoma. METHODS: HA and CD44 immunohistochemical assays were performed in the histopathologic specimens of 78 cases with ovarian adenocarcinoma and 24 cases with ovarian adenoma. Their expression in benign and malignant tumors with various histopathologic gradations were determined. Results were recorded as negative, weak positive, and strong positive. RESULTS: HA is mainly expressed in tumor stroma and extra-cellular mesenchyma, while cell membrane and cytoplasm were stained occasionally. In histologic sections, stronger expression was found in tumor stroma peripheral to carcinomatous nests. In total 102 specimens, positive HA expression in tumor stroma accounted for 71.27%. The positive rate in malignant tumor was 83.33%; the strong positive rate was 41.03%. However, the positive expression rate in benign tumor was 27.27%. The level of stromal HA expression increased along with histologic gradation. The expression level in serous adenocarcinoma was higher than that in other pathologic types. Expression of HA in stroma and expression of CD44 in the tumor cells were significantly correlated; and the correlation of HA expression with histologic gradations was better than that of CD44. However, the expression of HA in tumor cells was low and unrelated to pathologic types, histopathologic gradations, and CD44 expression. CONCLUSION: High level of HA in the stroma of ovarian adenocarcinoma is related to tumor histological gradations and pathologic types.

[Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in ectopic and eutopic endometrium].

OBJECTIVE: To study the expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in ectopic and eutopic endometrium in patients with endometriosis. METHODS: The expressions of MMP-9 and TIMP-1 in ectopic and eutopic endometrium were detected by immunohistochemistry streptavidin-biotin peroxidase (SP) method in 45 patients with endometriosis (study group) and in 32 patients with uterine fibroid (control group). RESULTS: In the ectopic and eutopic endometrium of group and in the control group endometrium, the expression of MMP-9 was respectively 0.381, 0.336 and 0.276; the expression of TIMP-1 was respectively 0.239, 0.253, 0.267. As a result, the ratio of MMP-9/TIMP-1 in ectopic and eutopic endometrium of study group and in the control group endometrium was respectively 1.594, 1.293, 1.034. The difference of MMP-9, MMP-9/TIMP-1 in ectopic and eutopic and the control group endometrium was markedly significant (P < 0.01 or P < 0.05). The difference of the expression of TIMP-1 between ectopic and the control group endometrium was also markedly significant (P < 0.01). Higher expression of MMP-9 and lower expression of TIMP-1 in ectopic endometrium and higher expression of MMP-9 in eutopic endometrium occurred in the whole menses period, in which higher expression of MMP-9 in ectopic endometrium than in eutopic endometrium only took place in proliferative phase. CONCLUSION: The change of expression of MMP-9 and TIMP-1 in ectopic endometrium may be related to the pathogenesis of endometriosis.

[Relationship between expression of matrix metalloproteinase (MMP-9) and tumor angiogenesis, cancer cell proliferation, invasion, and metastasis in invasive carcinoma of cervix].

BACKGROUND & OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) might plays an important role in regulating processes of tumor angiogenesis, invasion,and metastasis. The expression and clinical significance of MMP-9 in early invasive carcinoma of cervix was investigated. METHODS: Expression of MMP-9, microvessel density (MVD) labeled by CD(34) and proliferation index of cancer cells labeled by Ki-67 in 75 cases of early invasive carcinoma of cervix (ICC), 18 cases of cervical intraepithelial neoplasm (CIN), and 15 cases of normal cervical epithelium (NCE) were detected by immunohistochemistry SP method. RESULTS: MMP-9 was mainly expressed in the cellular membrane and/or cytoplasm in tumor cells,whereas expression of Ki-67 was mainly confined to the nuclei, and that of CD(34), to the vascular epithelial cells in tumor stroma. It was shown that positive rate of expression of MMP-9,Ki-67, and MVD increased remarkably from NCE to CIN,and then to ICC accordingly(P< 0.05). In ICC, MVD was positively related to the expression of MMP-9 (r=0.287, P<0.05). The expression of MMP-9 correlated with pelvic lymph node metastasis, intravascular and stromal infiltration, FIGO staging, histological grading,and Ki-67 expression (P< 0.05 or P< 0.01); but not correlated with patients age and histological types (P >0.05). In cases with pelvic lymph node metastasis, intravascular and deeper stroma infiltration, FIGO staging II, histological grade III and over-expression of Ki-67, positive rate of expression of MMP-9 was significantly higher than that in those without the conditions mentioned above (P< 0.05). CONCLUSION: In cervical carcinoma, MMP-9 may play an important role during tumor angiogenesis, proliferation of cancer cells, cancer invasion and metastasis. Over-expression of MMP-9 may result in great increase of tumor angiogenesis, rapid proliferation of cancer cells, cancer invasion and metastasis, but it is not the only decisive factor. Detection expression of MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.