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Objective: The PTEN tumor suppressor gene has been demonstrated to be inactivated in a variety of human tumors. In breast cancer, the PTEN gene mutation is not commonly found whereas loss of heterozygosity affecting the PTEN locus is frequently found. The aim of this study was to analyze PTEN protein expression in breast cancer and to evaluate the prognostic significance of PTEN protein expression. Methods: Paraffin-embedded sections ofinvasive ductal carcinoma of the breast were immunohistochemically stained for PTEN protein expression in 236 breast cancers. The immunohistochemical expression of breast cancer cells was judged to be either normal or reduced compared with the PTEN protein expression of the normal mammary gland. Results: The expression of PTEN protein was found to have decreased in 67 (28%) of 236 breast cancers. The reduced expression correlated with lymph node metastasis (p = 0.0371), but not with tumor size, nuclear grade, MIB-1 counts or p53 protein expression. Univariate analysis indicated that patients with a reduced PTEN expression had a shorter disease-free survival (DFS) than those with a normal PTEN expression (p = 0.0174). Univariate analyses also determined tumor size, lymph node metastases, nuclear grade, MIB-1 counts, p53 protein as well as PTEN protein expression to be significant factors for DFS, while multivariate analysis determined lymph node metastases and the MIB-1 counts to be independent significant factors for DFS. Conclusions: The inactivation of PTEN, demonstrated by a reduced expression of PTEN protein by immunohistochemistry, was found in about one third of all breast cancers. The reduced expression of PTEN protein correlated with lymph node metastases and a worse prognosis in the patients with breast cancer.

PurposeThe purpose of this study was to evaluate the correlation between histological invasiveness and the computed tomography (CT) value and size in pure ground-glass nodules (GGNs) to determine optimal “follow-up or resection” strategies.MethodsBetween 2001 and 2014, 78 resected, pure GGNs were retrospectively evaluated. The maximum diameter and CT value of pure GGNs were measured using a computer graphics support system.ResultsAll GGNs with a maximum diameter ≤10 mm and CT value ≤−600 Hounsfield units (HU) were considered to be noninvasive lesions, while 21 of 26 (81 %) with a maximum diameter >10 mm and CT value >−600 HU were considered to be invasive lesions. With respect to the correlation between each histological type and pure GGN with a maximum diameter ≤10 mm and CT value ≤−600 HU, the specificity was 90 % and the sensitivity and negative predictive value were both 100 % in atypical adenomatous hyperplasia (AAH), while the specificity was 58 % and the sensitivity and positive predictive value were 0 % in minimally invasive and invasive adenocarcinoma.ConclusionPure GGNs with a maximum diameter of ≤10 mm and CT value of ≤−600 HU are nearly always pre-invasive lesions; therefore, surgery should be carefully selected in such patients.

Angiopoietin (Ang) is a ligand for the endothelium-specific tyrosine kinase receptor Tie-2, while a shift in the Ang-1:Ang-2 expression ratio in favor of Ang-2 was found to be associated with tumor angiogenesis. In the present study, we analyzed the immunohistochemical expression of Ang-2 in a series of 198 breast cancers, in which VEGF expression and microvessel density (MVD) were previously determined. Ang-2 expression was negative in 24 (12%), positive in 50 (25%) and strongly positive in 124 (63%) of 198 cases. A significant correlation was found between Ang-2 and VEGF expressions (p=0.0004) and between Ang-2 expression and MVD (p=0.0006), while a high MVD was found in 10 (77%) of 13 tumors with a strongly positive VEGF and positive Ang-2 expression and in 40 (71%) of 56 tumors with a strongly positive VEGF and strongly positive Ang-2 expression. Although there was no difference in the disease free survival (DFS) stratified according to Ang-2 expression alone, the 69 patients with a strongly positive VEGF and a strongly positive or positive Ang-2 expression had a significantly (p=0.0316) worse DFS than those with other combinations of VEGF and Ang-2 expressions. A multivariate analysis indicated lymph node metastasis and MVD to be independently significant prognostic factors for DFS, while the combination of VEGF and Ang-2 expressions was not a significant factor for DFS. In conclusion, the Ang-2 expression was found to be closely correlated with VEGF expression and MVD in breast cancer, while a high MVD was frequently found in tumors with a high expression of both VEGF and Ang-2. The survival analysis demonstrated a high MVD, which was induced by a high expression of both VEGF and Ang-2, to therefore have a strong prognostic significance in breast cancer.

To evaluate the c-kit expression in breast cancer, 217 invasive ductal carcinomas of the breast were immunohistochemically stained for c-kit protein. The c-kit expression was positive in 59 (27%) of 217 tumours, while the c-kit expression was negative in 158 (73%) of 217 tumours. There was a significant correlation between a negative expression of the c-kit protein and lymph node metastasis (Po0.0001), and the incidence of a negative expression of the c-kit protein increased as the number of the metastatic lymph nodes increased (P ¼ 0.0003). The c-kit expression did not significantly correlate with the tumour size, nuclear grade, oestrogen receptor status, MIB-1 counts and p53 protein expression. A univariate analysis indicated the patients with the negative c-kit expression to have a worse disease-free survival (DFS) than those with the positive c-kit expression (P ¼ 0.0041), while a multivariate analysis determined lymph node metastases and the MIB-1 counts to be independently significant factors for DFS. In conclusion, a loss of the c-kit expression was found in about three-fourth of invasive ductal carcinoma of the breast and was associated with lymph node metastases. The prognostic implications of the c-kit expression seem to be due to fact that a loss of the c-kit expression is associated with an advanced stage of breast cancer.