Junko Kinoshita

Vascular endothelial growth factor-C (VEGF-C) expression in human colorectal cancer tissues

Vascular endothelial growth factor-C (VEGF-C) functions specifically to induce lymphangiogenesis. We examined the relationship between expression of VEGF-C and clinicopathological features in patients with colorectal cancer. The expression of VEGF-C in the 99 primary tumours and 18 metastatic lymph nodes from colorectal cancer patients was examined immunohistochemically. To verify VEGF-C mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out. The expression of VEGF-C correlated with lymphatic involvement, lymph nodes metastasis, and depth of invasion. On the other hand, correlations were nil with regard to gender of the patients, histologic type, venous involvement, and liver metastasis. The expression of VEGF-C in metastatic lymph nodes was fairly consistent with this expression in the primary tumour. Survival time was shorter for VEGF-C positive groups than for VEGF-C negative ones, but with no statistically significant difference. RT-PCR findings revealed that the expression of VEGF-C mRNA correlated mostly with that of VEGF-C protein expression. VEGF-C may play an important role in lymphatic spread of colorectal cancer.

Clinical significance of vascular endothelial growth factor‐C (VEGF‐C) in breast cancer

Vascular endothelial growth factor‐C (VEGF‐C) is a specific ligand which induces lymphangiogenesis. We examined the expression of VEGF‐C protein to determine its role in the progression of breast cancer. Immunohistochemical analysis revealed that VEGF‐C was overexpressed in 39 of 98 breast cancer specimens (39.8%) but not in adjacent normal mammary glands. The expression of VEGF‐C showed a significant correlation with lymphatic vessel invasion (p=0.0004). It is noteworthy that the 5‐year disease free survival rate of the VEGF‐C positive group was significantly poorer than that of negative group (p=0.0356). We suggest that as expression of VEGF‐C is not implicated in lymphatic spread, it may prove to be a promising marker to predict the recurrence of breast cancer.

A novel variant of WISP1 lacking a von Willebrand type C module overexpressed in scirrhous gastric carcinoma

Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is known of the molecular pathogenesis of this disease. Members of the emerging family of the CCN gene (for connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles in human fibrotic disorders and cancer progression. Using targeted differential displays, we identified a novel variant of the CCN family member WISP1 (Wnt-induced secreted protein 1), named WISP1v, as overexpressed in scirrhous gastric carcinomas. Predicted protein of the WISP1v completely lacks a module of Von Willebrand type C that is thought to participate in protein complex formation. Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a striking cellular transformation and rapid piling-up growth. It is noteworthy that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric carcinoma cells, while wild-type WISP1 had no such potential. These findings suggest that CCN protein WISP1v is involved in the aggressive progression of scirrhous gastric carcinoma.

Prognostic significance of the coexpression of p53 protein and c-erbB2 in breast cancer.

BACKGROUND The expressions of p53 protein and c-erbB2 have been thoroughly analyzed as prognostic factors for breast cancer. However, the prognostic significance of the coexpression of p53 protein and c-erbB2 remains controversial. METHODS The immunohistochemical expression of p53 protein and c-erbB2 was evaluated in 242 women with breast cancer. RESULTS According to the combination of p53 protein and c-erbB2, a group negative for both (125 cases), a group positive for either one of these two parameters (99 cases) and a group positive for both (18 cases) were identified. The group positive for one factor had a significantly (P = 0.0045) worse disease-free survival (DFS) than the group negative for both, while the group positive for both had a significantly (P = 0.0023) worse DFS than the group positive for one factor. A multivariate analysis indicated that the relative risk of p53 protein alone and cerbB2 alone was 2.18 and 2.93, respectively, while the relative risk of the group positive for one factor and the group positive for both was 2.29 and 6.37, respectively . CONCLUSIONS Breast cancer with a coexpression of p53 protein and c-erbB2 was thus found to have a more significant prognostic value than those with a positive expression for either of these two biological parameters, while the prognostic significance of these two parameters themselves remained independent of each other.

Endoscopic extirpation of benign breast tumors using an extramammary approach

BACKGROUND Skin incision has been made directly in the breast for treatment of benign breast tumor in spite of the young age of the patient population. METHODS Small incisions (12 mm, 5 mm, and 2 mm) were made in the extramammary line, and the benign tumors (diagnosed by imaging and aspiration needle cytology) were endoscopically extirpated. RESULTS The mean age of 36 patients was 27.6 years, and the mean mass size was 3.6 cm (7 masses at maximum). The average operation time per mass was 2.6 hours in the first 18 operations and 1.4 hours in the latter 19 operations. Overall blood loss was 19 mL. Postoperative complications were seen in 2 patients: an extended subcutaneous emphysema due to excessive CO2 gas inflation and a mild burn, both of which were reversible. All patients were extremely satisfied with the cosmetic results of the procedure. CONCLUSIONS Endoscopic removal by the extramammary approach is the best option for benign breast tumors considering the patients age and the excellent cosmetic results.

Sex hormone-receptor-negative tumors have a higher proliferative activity than sex hormone-receptor-positive tumors in human adenocarcinomas of the gastrointestinal tract

To determine whether a correlation exists between hormone receptors and their proliferative activities, the levels of estrogen receptors (ER) and progesterone receptors (PgR) in surgical specimens from 23 patients with gastric cancer and from 32 patients with colorectal cancer were investigated using an enzyme immunoassay. These values were examined in relation to the parameters of cell kinetics determined by DNA flow cytometry. When the cutoff value was determined as 2.0 fmol/mg of cytosolic protein, ER and PgR were found in 13 (56%) and 6 (26%) of the 23 patients with gastric cancer, respectively, and in 10 (31%) and 10 (31%) of the 32 patients with colorectal cancer, respectively. There was a significant correlation in the expressions of ER between the cancer tissues and normal mucosa (P=0.040). Although the expressions of ER or PgR were apparently not related to pathological status, better correlations of hormone receptor-negative tumors with increased hyperaneuploid levels were evident. According to a multiple regression analysis, ER levels significantly correlated with changes in the DNA index (P=0.041) and in the heterogeneity index score (HIS) (P=0.034). Thus, sex hormone receptors proved to be relevant factors associated with the proliferative activity of adenocarcinoma of the gastrointestinal tract. These findings indicate that the expression of hormone receptors provides pertinent biological information required to determine adequate therapeutic regimens in patients with gastrointestinal cancer.

Comparison of the Immunohistochemical Expression of EGFR, c-erbB2 and p53 Protein between Primary and Recurrent Breast Cancer

BackgroundAlthough various biological parameters have been evaluated as predictors of the response to chemohormonal therapy for breast cancer, few studies have comparied the biological parameters of the primary and recurrent breast cancers.Patients and MethodsThe immunohistochemical expression of epidermal growth factor receptor (EGFR), c-erbB2 and p53 protein were analyzed on both primary and matching recurrent lesions from 42 patients with breast cancer.ResultsEGFR and c-erbB2 expression were concordant between the primary and matching recurrent lesion in 27 (90%) of 30 cases in which EGFR was evaluated and in all (100%) 12 cases in which c-erbB2 was evaluated. Twelve (67%) of 18 cases in which p53 protein was evaluated showed concordance of p53 protein expression between the primary and recurrent lesions, while 6 other cases did not. The intensity of the immunoreactivity of p53 protein was 10-50% staining in 5 of these 6 cases, while only one case showed greater than 50% staining of p53 protein in the primary lesion and negative staining in the matching recurrent lesion.ConclusionEGFR and c-erbB2 immunoreactivity were concordant between the primary and matching recurrent lesions in the majority of the breast cancer cases. In addition, some cases were not concordant regarding the intensity of immunoreactivity for p53 protein, whereas few cases showed both a strong positivity and negative finding for p53 protein between the primary and matching recurrent lesions.

Prognostic Significance of the Combination of Biological Parameters in Breast Cancer

Abstract.To evaluate whether the combination of biological parameters increases their prognostic value, the expression of epidermal growth factor receptor (EGFR), DNA ploidy, and estrogen receptor (ER) status were analyzed on 998 patients with breast cancer. Poor findings for each biological parameter were positive for EGFR, aneuploid for DNA ploidy, and negative for ER. According to the number of poor findings in these three parameters, the groups with none (309 cases), one (377 cases), two (161 cases), and three (151 cases) poor findings were classified. A significant (P < 0.0001) difference was found in the disease-free survival (DFS) among the four groups. A multivariate analysis indicated the combination of three biological parameters to be an independently significant factor for DFS, while the relative risk gradually increased as the number of poor findings increased. In conclusion, the present study indicated a gradual increase in the prognostic significance as the number of combined biological parameters increased.

Histological classification of invasive ductal carcinoma and the biological parameters in breast cancer

BackgroundThe histological classification of invasive ductal carcinoma proposed by the Japanese Breast Cancer Society is based on the appearance of breast cancer invasion. However, few studies have been done to clarify the relationship between the histological classification and other parameters that represent the biological characteristics of individual breast cancer cells.Materials and MethodsWe analyzed 1,025 invasive ductal carcinomas, consisting of 424 papillotubular, 330 solid-tubular and 271 scirrhous cases, with regard to the status of estrogen receptor (ER), progesterone receptor (PgR), DNA ploidy, epidermal growth factor receptor (EGFR) and p53 protein.ResultsAbsence of ER and PgR, aneuploidy, EGFR positivity and p53 protein positivity were all observed significantly more frequently in solid-tubular tumors than in the other two types. In addition, the number of abnormal features with regard to these 5 biological parameters was also significantly higher in solid-tubular tumors than in the other two types.ConclusionAbnormalities in the biological parameters listed above were frequently found in the solid-tubular type of invasive ductal carcinoma.