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ABSTRACT: A wide range of frequencies has been reported for blood vessel invasion (BVI) among patients with breast cancer, however, the prognostic significance of BVI remains controversial. Three hundred ninety-eight Japanese patients with breast cancer, operated on during the period between 1971 and 1987, were studied. We investigated five factors, including BVI, lymph-node status (n), clinical tumor size (T), histological grade (HG), and tumor necrosis (TN), followed for a median of 10 years. BVI was detected by hematoxylin and eosin (HE) staining and both factor VIII-related antigen and elastica van Gieson staining. BVI detected by HE staining alone was defined as BVIh. The subtypes of BVI were classified as follows: BVI e, BVI detected only by elastica van Gieson staining; BVI f, BVI detected only by factor VIII-related antigen staining; and BVI e/f, BVI detected by both factor VIII-related antigen and elastica van Gieson staining. BVI-positive tumors were defined as lesions showing BVI e, BVI f, or BVI e/f. BVI and BVIh were presented in 27.4%, 6.5% of all cases, respectively. The mean diameters of the calibers of BVI e, BVI f, and BVI e/f were 141.9+/-80.5 microm, 61.0+/-37.4 microm, 136.0+/-102.0 microm, respectively (P<0.0001). Seventy-three patients (18.3%) had recurrence and 60 patients (15.1%) died of breast cancer. Univariate analysis showed that BVIh (P <0.0001), BVI (P<0.0001), n, T, and HG were significantly predictive of 20-year RFS and OS. Multivariate analysis showed that BVI (P<0.0001, P = 0.0088, respectively), n, T, and HG were all significant and independent prognostic factors for RFS and OS. On the other hand, BVIh was an independent factor for RFS (P = 0.0475), but of borderline significance for OS (P = 0.0506). When stratified by BVI, BVI e, and BVI e/f were significantly predictive of 20-year RFS or OS (P < 0.0001). We can confirm BVI, especially BVI e and BVI e/f, are significant independent prognostic factors associated with long-term survival in Japanese breast cancer patients.
Breast Cancer Research and Treatment 05/2002; 73(1):1-12. · 4.43 Impact Factor
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ABSTRACT: Angiogenesis, as assessed by microvessels, has been a common prognostic indicator for breast cancer in the last decade. However, the significance of angiogenesis remains controversial. This is a retrospective study of 377 Japanese patients selected from 663 breast cancer patients operated on between 1971 and 1987. To evaluate an objective method to quantify microvessel density in angiogenesis, we employed average microvessel count (AMC) per square millimeter. We investigated five factors: angiogenesis, lymph-node status (n), clinical tumor size (T), histological grade (HG), and tumor necrosis (TN), followed for a median of 10 years. Sixty-seven patients (17.8%) had recurrence and 54 patients (14.3%) died of breast cancer. Univariate analysis showed that n, T, HG, and AMC (P=0.0020) were significantly predictive of 20-year relapse-free survival (RFS). n, T, and HG were significantly associated with 20-year overall survival (OS) but AMC was borderline significant (P=0.0630). Multivariate analysis for RFS and OS showed that n, T, HG, and AMC (PP=0.0033, respectively) were all significant and independent prognostic factors. When stratified by T or n, a significant impact of AMC on RFS or OS was seen both in patients with T2 and T3 carcinomas or in node-negative patients, but not in T1 or node-positive patients. Thus, we can confirm angiogenesis as a significant independent prognostic factor associated with long-term survival in Japanese breast cancer patients, especially in node-negative patients and in patients with T2 and T3 carcinomas.
Breast Cancer Research and Treatment 10/2001; 70(1):65-74. · 4.43 Impact Factor
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Takao Kato,
Tsunehito Kimura,
Nobue Takami,
Ryuhei Miyakawa,
Schinichi Tanaka,
Hiroshi Muraki,
Takako Kamio,
Akiho Fujii,
Kazuko Yamamoto,
Shingo Kameoka,
Toshio Nishikawa,
Takeshi Kasajima
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ABSTRACT: 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.
Breast Cancer 01/1999; 6(4):370-377. · 1.36 Impact Factor
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ABSTRACT: This study was designed to evaluate the prognostic importance of p53, mitosis, apoptosis and necrosis with long-term follow-up in Japanese patients with breast cancer. Four hundred and twenty-two patients with breast cancer were studied. We investigated 7 factors, including p53, mitotic index (MI), apoptotic index (AI), necrosis, lymph-node status (n), clinical tumor size (T) and lymphatic vessel invasion, followed for a median of 10 years. p53 accumulation was found in 30.1%, MI in 35.2%, AI in 36.3% and necrosis in 38.5%. p53 accumulation was correlated with MI (p = 0.0324), AI (p = 0.0010), necrosis (p = 0.0003), T (p = 0.0320), n (p < 0.0001), estrogen receptor (p = 0.0005) and progesterone receptor (p = 0.0287). Univariate analysis showed that p53, MI and necrosis were significantly predictive of 20-year overall survival (OS) or of 20-year relapse-free survival (RFS) (p < 0.0001 or p = 0.0003, p< 0.0001 or p < 0.0001 and p = 0.0131 or p = 0.0068, respectively), but AI was not. Multivariate analysis showed that p53 was an independent prognostic factor with RFS in all the patients, especially, with relapse-free survival (RFS) in the patients with T1 and with RFS and overall survival (OS) in the patients with a node-negative tumor. MI was an independent prognostic factor with OS in all the patients and with RFS and OS in the patients with a node-negative tumor. However, AI and necrosis were not independent predictors.
Anticancer research 22(2B):1105-12. · 1.73 Impact Factor
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ABSTRACT: This study was designed to evaluate the prognostic importance of c-erbB-2 and proliferating cell nuclear antigen (PCNA) with long-term follow-up in Japanese patients with breast cancer. Four hundred and eight patients with breast cancer were studied. We investigated 6 factors, including c-erbB-2, PCNA, lymph-node status (n), clinical tumor size (T), histological grade (HG) and lymphatic vessel invasion, followed for a median of 10 years. c-erbB-2 overexpression was found in 35.0% and PCNA in 43.1% of the carcinomas. c-erbB-2 positivity was correlated with PCNA (p < 0.0001), n (p<0.0001), T (p = 0.0016), and HG (p = 0.0110). Univariate analysis showed that c-erbB-2 was significantly predictive of 20-year overall survival (OS) (p = 0.0247), but not of 20-year relapse-free survival (RFS). PCNA was significantly associated with 20-year RFS and OS (p <0.0001, p < 0.0001, respectively). Multivariate analysis showed that PCNA was an independent prognostic factor in node-negative patients, but c-erbB-2 and PCNA were not independent prognostic indicators in all patients. Although c-erbB-2 expression and PCNA were obviously important from a biological standpoint, they were not recognized as independent molecular markers.
Anticancer research 22(2B):1097-103. · 1.73 Impact Factor
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