Kazuko Yamamoto

The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long‐term survival in Japanese patients with breast cancer

The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49–56, 1997. The follow‐up period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), c‐erbB‐2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1–20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIII‐related antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirty‐one patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p < 0.0001), histological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and c‐erbB‐2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.

Clinicopathologic Study of Angiogenesis in Japanese Patients with Breast Cancer

Abstract. To evaluate the clinicopathologic significance of angiogenesis as a prognostic factor and the objective methods for evaluating angiogenesis, we immunohistochemically stained a representative section of breast tumors with factor VIII-related antigen staining. There were 109 patients with primary breast cancer from 1971 to 1979. The two methods of identifying angiogenesis were the average microvessel count per square millimeter (AMC) and the highest microvessel count per square millimeter (HMC). There was no relation between microvessel count (AMC or HMC) or age, menopausal status, clinical tumor size (T), histologic classification, nuclear grade, node status, histologic grade (HG), mitosis index, or lymphatic invasion (LI). There was a relation between microvessel count and blood vessel invasion (BVI) (HMC:p = 0.0007) and tumor necrosis (TN) (HMC:p = 0.0050). Univariate analysis showed that AMC or HMC was a statistically significant predictor of overall survival in all patients (p = 0.0086 andp = 0.0307, respectively). Multivariate analysis showed that AMC was an independent predictor of node status when we fitted a model with node status, BVI, and either AMC or HMC; but HMC was not independent. However, when we fitted a model including all 11 of the other indicators and AMC or HMC, the node status, HG, and LI were independent predictors, but AMC and HMC were not. Although AMC was a better method than HMC for evaluating angiogenesis, we cannot confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients.

Pathologic Evaluation of Surgical Margins and Local Recurrences after Breast-conserving Surgery without Irradiation

This study was undertaken to evaluate the status of margins of the excised breast tissue using our own method. We also determined the indications for breast-conserving surgery without irradiation by examining the characteristics of patients with local recurrence and comparing relapse-free survival (RFS) and overall survival (OS) of patients who underwent wide excision without irradiation with those of 267 patients who underwent total mastectomy. Eighty-two patients with a 3 cm diameter or less invasive carcinoma were treated with wide excision and axillary dissection between 1987 and 1996. Patients who histologically had four or more axillary lymph node metastases, positive pathologic margins, or a high degree of in situ ductal carcinoma around the main tumor in consecutive step-sections were excluded from this study. During a median follow-up of 6 years (range 2–11 years), six patients (7.3%) had local recurrence and five (6.0%) had regional or distant recurrences as their site of first failure. At 11 years the life-table values for RFS and OS for the wide excision-treated group were 84.7% and 92.1%, respectively, compared with 85.0% and 90.0%, respectively, for patients treated by total mastectomy. RFS and OS were similar in the two treatment groups. Results in the present study indicate that if the patients treated by breast-conserving surgery are carefully selected and there are no foci in the pathologic margins, there is a low degree of in situ ductal carcinoma around the tumor, and no multicentricity, it might be unnecessary to administer radiation therapy.

Clinicopathologic Features Associated with Long-Term Survival in Node-Negative Breast Cancer Patients

This study was undertaken to assess blood vessel invasion (BVI) and other histologic features to determine the best method of histologic prognosis in node-negative breast cancer patients. The prognostic significance of the clinicopathological findings was evaluated in 70 patients with nodenegative breast cancer among 135 patients operated on between 1971 and 1981. The prognostic factors investigated included BVI, peritumor lymphatic invasion, clinical tumor size, nuclear grade, histological grade, mitotic grade, and tumor necrosis. BVI was detected by factor VIII-related antigen and elastica van Gieson staining. BVI-negative patients had a 20-year cumulative survival of 93.7%, versus 74.7% for BVI-positive patients (P=0.0294). The clinical tumor size also correlated well with prognosis (P<0.0001). However, the other histologic features did not correlate with a poor prognosis. Moreover, we retrospectively examined the effect of postoperative chemotherapy for patients with BVI and T3, and the prognosis of those given chemotherapy seemed to be better than that of those who were not. Tumors measuring more than 51 mm and BVI may thus represent adverse prognostic factors in node-negative breast cancer patients.

New prognostic factors associated with long-term survival in node-negative breast cancer patients

BackgroundThis study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer.Patients and MethodsTwo hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using permanent-section immunohistochemistry, clinical tumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20).ResultsTwenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multivariate analysis showed that clinical tumor size (P=0.0003), angiogenesis (P=0.0003), PCNA (P= 0.0064), and HG (P=0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P=0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor.ConclusionPCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.