PAX8 is a potential marker for the diagnosis of primary epithelial ovarian cancer.

The present study aimed to investigate the clinical significance of paired-box 8 (PAX8) in primary epithelial ovarian cancer (PEOC). Using immunohistochemical (IHC) staining, the expression of PAX8 in 60 patients with PEOC, 20 patients with ovarian benign lesions and 10 patients with metastatic ovarian cancer (MOC), was examined based on the clinicopathological profiles of the patients. The correlation between PAX8 expression and the clinicopathological parameters or prognosis of patients was statistically analyzed. PAX8 was revealed to be highly expressed in PEOC, but not in MOC, as indicated by IHC staining. The rate of positivity of PAX8 in PEOC was 92% (57/60) with no significant difference of PAX8 expression found between the various pathological types of PEOC (P=0.871). The rate of positivity of PAX8 in ovarian benign tumors was 85%, demonstrating no significant difference in comparison with that of PEOC (P=0.761). PAX8 staining and statistical analysis revealed that the higher the grade of PEOC, the less the cancer cell had differentiated (P=0.033) and the more the cancer had advanced according to International Federation of Gynaecological Oncologists (FIGO) staging (P=0.003). Survival rate statistics showed that PEOC patients with higher PAX8 expression exhibited a shorter postoperative survival rate (P=0.009). PAX8 was specifically expressed in PEOC, and its expression level was associated with the degree of cancer cell differentiation, FIGO stage, and survival rate, indicating that PAX8 is a potential marker for the diagnosis of PEOC.

Thin-section computed tomography-histopathologic comparisons of pulmonary focal interstitial fibrosis, atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma with pure ground-glass opacity.

OBJECTIVE: To retrospectively compare focal interstitial fibrosis (FIF), atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA) with pure ground-glass opacity (GGO) using thin-section computed tomography (CT). MATERIALS AND METHODS: Sixty pathologically confirmed cases were reviewed including 7 cases of FIF, 17 of AAH, 23of AIS, and 13 of MIA. All nodules kept pure ground glass appearances before surgical resection and their last time of thin-section CT imaging data before operation were collected. Differences of patient demographics and CT features were compared among these four types of lesions. RESULTS: FIF occurred more frequently in males and smokers while the others occurred more frequently in female nonsmokers. Nodule size was significant larger in MIA (P<0.001, cut-off value=7.5mm). Nodule shape (P=0.045), margin characteristics (P<0.001), the presence of pleural indentation (P=0.032), and vascular ingress (P<0.001) were significant factors that differentiated the 4 groups. A concave margin was only demonstrated in a high proportion of FIF at 85.7% (P=0.002). There were no significant differences (all P>0.05) in age, malignant history, attenuation value, location, and presence of bubble-like lucency. CONCLUSION: A nodule size >7.5mm increases the possibility of MIA. A concave margin could be useful for differentiation of FIF from the other malignant or pre-malignant GGO nodules. The presence of spiculation or pleural indentation may preclude the diagnosis of AAH.

Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma.

BACKGROUND: To investigate on the expressions and the clinical significances of hepatocyte growth factor receptor (c-MET), phosphorylated c-MET (p-MET) and e2f-1 transcription factor in primary lesion of gastric adenocarcinoma (GC). METHOD: Tissue samples from the primary lesion of GC in patients who accepted D2/D3 radical gastrectomy with R0/R1 resection were stained by immunohistochemistry of c-MET, p-MET, e2f-1 and Ki-67. The univariate and the multivariate analyses involving in clinicopathological parameters and prognostic factors were evaluated. RESULTS: The positivity rates for c-MET (66.12%, 80 cases/121 cases), p-MET (59.50%, 72 cases/121 cases), e2f-1 (38.84%, 47 cases/121 cases) and Ki-67 (72.73%, 88 cases/121 cases) in primary lesion of GC was significantly higher than that in non-cancerous tissue at 5 cm places far from the margin of primary lesion (P < 0.05, respectively). The deeper tumor invasion, the severer lymph node metastasis, the later stage of TNM and the higher expression of Ki-67 was respectively an independent risk factor for the higher expression of c-MET or p-MET, but the younger age and the shorter survival time was an independent risk factor for the higher expression of e2f-1 respectively. Survival analysis showed that the worse prognosis could be observed in the patients with the combination of both c-MET-positive and e2f-1-negative (P = 0.038) or both p-MET-positive and e2f-1-negative (P = 0.042). Cox analysis demonstrated that the severer lymphatic node metastasis and the higher positivity rate of c-MET, p-MET or e2f-1 were an independent prognosis factor respectively. The higher expression of e2f-1 was identified in patients with Stage I-II, which correlated with a shorter survival time. Survival analysis also revealed that the prognosis of patients with positive expression of e2f-1 at Stage I-II was significantly worse than that in patients with negative expression of e2f-1 (χ2 = 13.437, P = 0.001). However, in the cases with Stage III-IV, no significant difference could be identified in the prognostic comparison between positive and negative expressions of e2f-1. CONCLUSIONS: The expression of c-MET or p-MET is an independent prognosis factor. It has been observed that the higher expression of e2f-1 occurred in the early stages while the lower expression of it in the later stages in GC.

Expression and significances of contactin-1 in human gastric cancer.

Background. This study aimed at determining the relationship between vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3), and contactin-1 (CNTN-1) expression in gastric cancer (GC). Methods. The expression level of CNTN-1 mRNA and CNTN-1 protein of 33 cases was determined using RT-PCR and Western Blot. And 105 cases were immunohistochemically examined for VEGF-C, VEGFR-3, and CNTN-1 expressions. Assessment of lymphatic vessel density (LVD) was also performed by D2-40 immunostaining. Then we analyzed the relationships between VEGF-C, VEGFR-3, and CNTN-1, as well as their correlations with clinicopathologic features, LVD, and survival time. Results. The positivity rate of VEGF-C, VEGFR-3, and CNTN-1 in primary tumor was 56.19%, 64.76%, and 58.09%. The expression of CNTN-1 significantly correlated with VEGF-C (P < 0.001) and VEGFR-3 (P < 0.001). All of them were closely related to TNM stage, lymphatic invasion, and lymph node involvement (P < 0.05). LVD was significantly correlated with VEGF-C (P = 0.001), VEGFR-3 (P = 0.011), and CNTN-1 expression (P < 0.001). VEGF-C, VEGFR-3, and CNTN-1 expression significantly associated with poorer prognosis (P < 0.001, P = 0.034, P = 0.012, resp.). Conclusion. CNTN-1 associated with VEGF-C and VEGFR-3 expression in GC. All of them correlated with lymphatic metastasis, which might play an important role in the lymphatic invasion via lymphangiogenesis pathway in GC.

Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion, and lymph node micrometastasis in gastric cancer.

BACKGROUND: This study aimed to evaluate the clinical significance of lymphangiogenesis, lymph vessel invasion (LVI), and lymph node (LN) micrometastasis (LNMM) in patients with gastric cancer. METHODS: The influences of the expression levels of LVI, lymph vessel density (LVD) by D2-40 immunohistochemical (IHC) staining (n=68), LNMM (including CK 20 and CK pan immunostainings, n=51) on the clinicopathologic profiles and the prognosis were analyzed. RESULTS: The higher positive rate of LVI-IHC was related to deeper invasion (P=0.044), later TNM stage (P=0.003), and more extensive LN metastasis (LNM, P=0.000). The level of LVD was significantly associated with venous invasion (P=0.037), later TNM stage (P=0.020), positive LVI-HE (P=0.040), positive LVI-IHC status (P=0.001), and severer LNM (P=0.001). Better prognosis in LVI negative group than LVI positive group has been identified. The survival rate of the group with LVD≥15/field was significantly lower than that in the group with LVD≤14/field (P=0.032). Invasion depth, N stage, LNM, blood vessel invasion, or LVI was respectively an independent prognostic factor to 3-y survival rate. The incidence of patients with LNM and metastasized LNs increased respectively from 74.5% (38/51) by HE staining to 88.2% (45/51) by CK immunostaining and from 32.0% (253/791) to 41.5% (328/791) (P=0.001). The increment of LNMM was correlated to larger tumor diameter (P=0.001), deeper invasion (P=0.018), LNM (P=0.001) and later TNM stage (P=0.012), positive LVI (P=0.04). Meanwhile, the evaluation on LNMM revealed the migration of LN stage (N(0)→N(1) in seven patients, N(1)→N(2) in six patients, and N(2)→N(3) in one patient), and TNM stage (I(b)→II in four patients, II→III(a) in 4 patients, III(a)→III(b) in 3 patients, and III(b)→IV in one patient). Survival analysis demonstrated that better prognosis in patients without LNM and/or LNMM. CONCLUSION: Our immunohistochemical analyses using antibodies of D2-40 and CK, including both CK 20 and CK pan, detected a higher incidence of LVIs and LNMs in gastric cancer specimens. This study shows close correlations among lymphangiogenesis related factors, such as LVI, LVD, and LNMM, and patients' prognosis after surgery. Therefore, immunohistochemical evaluations of these factors could be used for the accurate determination of tumor aggressiveness.

Clinical significance of changes in tumor markers, extracellular matrix, MMP-9 and VEGF in patients with gastric carcinoma.

BACKGROUND/AIMS: The aim of this study was to evaluate the prognostic significance of some serum tumor marker level, extracellular matrix (ECM), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) in patients with gastric cancer. METHODOLOGY: The serum tumor markers included CEA, CA50 and CA19-9, ECM included laminin (LN), hyaluronic acid (HA), and collagen type III and IV were measured in 40 patients with gastric carcinoma and 20 matched healthy controls by radioimmunoassay. MMP-9, VEGF and MVD were measured with immunohistochemical methods and the computer image analyzer. Microvascular density (MVD) in tissues of patients with gastric carcinoma was detected. RESULTS: The levels of CEA, CA50, CA19-9, HA, LN and collagen type IV in the patients with metastasis were significantly higher than those in the patients without metastasis (p < 0.05). The expression of MMP-9 and collage type IV in the patients with metastasis and poorly differentiated carcinomas were significantly higher than those in the patients without metastasis whose tumors were well/moderately differentiated (p < 0.05). CONCLUSIONS: CEA, CA50, CA19-9, HA, LN and collagen type IV levels can be used as a signal of metastasis and disease progression in patients with gastric carcinoma. When a gastric carcinoma expresses a high level of MMP-9 and VEGF with high MVD, the power of infiltration and metastasis of the gastric carcinoma is enhanced.