C-erbB-2, p53, and nm23 gene product expression in breast cancer in young women: Immunohistochemical analysis and clinicopathologic correlation

We studied c-erbB-2, p53, and nm23 gene products in 112 primary breast carcinomas. Fifty patients were aged 35 years or younger, and 62 were aged 36 to 50. Clinicopathological criteria including clinical stage, hormone receptor status, histological types, histological grades, and lymph node status, were reviewed. Disease-free survival (DFS) and overall survival (OS) were analyzed. Immunohistochemical findings were assessed semiquantitatively. Correlation between clinicopathological criteria, survival data, and immunohistochemical findings have been made. Patients aged younger than 35 years with stage I to II disease had a shorter DFS (P = .03) than older patients. However, no other clinicopathological finding was associated with age. Neither was there association between age and c-erbB-2, p53, or nm23 patterns of expression. p53 positivity was associated with high histological grade (P = .003) and with progesterone receptor negativity (P = .045). Nm23 nuclear positivity was associated with early clinical stages (P = .011) and with absence of axillary lymph node metastasis (P = .007). p53 and c-erbB-2 overexpression were associated with shorter OS while nm23 nuclear positivity was associated with longer OS in univariate and multivariate analyses. Univariate analyses showed that c-erbB-2 or nm23 were potentially important prognostic factors in women aged 35 years or younger while p53 was associated with prognosis in women aged 36 to 50. Cox model analysis indicated that c-erbB-2 alone was associated with prognosis in women 35 years and younger, whereas p53 alone was associated with prognosis in 36-to 50-year-old women. These results suggest that breast cancer in the youngest women has some biological specificity.     

EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival.

One hundred patients with breast carcinoma followed for 7-11 years were included in the present study of EGFR family members, using immunohistochemistry and RT-PCR. By immunohistochemistry, 36%, 27%, 26%, and 82% of the tumours were positive for EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. All the immunoreactive tumours were confirmed positive by RT-PCR. Tumour size, histological grade, lymph node status, S-phase fraction, and stage were confirmed to be significantly associated with both disease-free and cancer-specific survival in the present study. Methods of treatment, histological type, and ploidy had no significant effect on survival. Statistical analysis of EGFR family members in these tumours showed a significant association between c-erbB-2 expression and reduced disease-free and cancer-specific survival. c-erbB-4 expression was associated with a more favourable outcome. Co-expression of c-erbB-2 and EGFR was associated with a worse prognosis. c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. In conclusion, c-erbB-2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. However, c-erbB-4 antagonizes the c-erbB-2 effect on clinical course in breast carcinomas. To achieve best results with immunotherapy against the c-erbB-2 receptor, clarifying the status of c-erbB-4 expression may be of significance.     

Long-term survival in breast cancer related to overexpression of the c-erbB-2 oncoprotein: an immunohistochemical study using monoclonal antibody NCL-CB11.

In a previous series we have shown poor short-term (3-5 years) survival for patients with tumours overexpressing the c-erbB-2 oncoprotein. In this study we employed archival paraffin-embedded tissue from patients who underwent mastectomy 10-12 years prior to assessment (n = 187). Immunohistochemical staining was carried out by an indirect immunoperoxidase technique using the novel monoclonal antibody NCL-CB11. Tumours were scored according to intensity of membrane staining. Patient and tumour information was obtained by scrutiny of clinical records. Survival analysis was carried out for both time to relapse and time to death, using the log rank test. Patients with tumours demonstrating intense membrane staining had a poor prognosis compared with the rest, with a steeply sloped survival curve over the first 4 years; the survival difference was still evident at 12 years follow-up (P less than 0.001). The survival advantage for c-erbB-2 negative patients was maintained in lymph node negative patients (P less than 0.001). However, c-erbB-2 status did not influence survival in the node positive group, where all patients had a uniformly poor outlook. These results applied to both time to relapse and time to death. In conclusion, c-erbB-2 status, determined using NCL-CB11, is a powerful prognostic indicator, defining in particular node negative patients with a particularly poor prognosis, and for whom alternative therapeutic strategies may be appropriate.     

Effect of Chemotherapy for Luminal A Breast Cancer

Background

The addition of chemotherapy to endocrine therapy for luminal A breast cancer generally provides little benefit. However, the least benefit of chemotherapy in all patients with luminal A breast cancer is controversial.

Methods

This was a retrospective study of 140 patients with luminal A breast cancer who underwent surgery at Tottori University Hospital between 2001 and 2010. Luminal A breast cancer was defined as positive for estrogen receptors and/or progesterone receptors and negative for human epidermal growth factor 2. Postoperative endocrine therapy was given to all patients. The prognostic values of age, tumor size, presence of lymphovascular invasion and lymph node status were evaluated. In addition, the prognostic value of chemotherapy for patients with identified risk factors affecting relapse-free survival and overall survival was evaluated.

Results

Tumor size greater than 2 cm and positive lymph node status were factors significantly affecting relapse-free survival. There were no factors significantly affecting overall survival. There was no significant difference in the relapse-free survival of patients with tumor size greater than 2 cm and/or positive lymph node status who either received chemotherapy or not. However, the relapse event was earlier in patients with tumor size greater than 2 cm and positive lymph node status who did not receive chemotherapy than in those who received chemotherapy.

Conclusion

Chemotherapy could provide little benefit to patients with luminal A breast cancer. However, chemotherapy may bring them longer relapse-free periods.     

The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma

BACKGROUND: Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients. Objective: To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma. METHODS: The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis. RESULTS: 189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general. CONCLUSIONS: IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.     

Computer-generated nuclear features compared with axillary lymph node status and tumor size as indicators of breast cancer survival

The extent to which malignant cells deviate from normal is generally accepted to be a prognostic indicator. However, assessing the degree of deviation has been subjective and poorly reproducible. Our goal is to develop a computer program for objectively measuring nuclear size, shape, and texture from histologic slides and to make the program available on the Internet. We used this program to analyze 353 histologic sections obtained from patients with invasive breast cancer who were diagnosed and treated from 1981 through 1995 and who had determinable outcomes. The median follow-up was 8.3 years. We compared the relationship of survival with our computer-derived nuclear features versus axillary lymph node status and tumor size. We believe that our results are generally applicable because our patient survival, when stratified by lymph node status, was similar to that of the 24,000 breast cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results program. In multivariate analysis, the strongest prognostic factor was the largest nuclear area, followed by tumor size and the extent of axillary lymph node involvement. The mean area of the 3 largest nuclei when combined with tumor size identified 30% of all breast cancer patients who had an 87% 15-year breast cancer-specific survival. Inclusion of lymph node status added little to this 2-factor model. Routine axillary lymph node surgery for prognostic purposes may become unnecessary, because nuclear features may provide sufficient information.     

The significance of c-erbB-2 overexpression and p53 expression in patients with axillary lymph node--negative breast cancer: a tissue microarray study

We conducted this study to examine whether the expression of c-erbB-2 and p53 is the prognostic indicator for patients with early-stage breast cancer in which axillary lymph node metastasis is absent. We examined 326 patients with early-stage breast cancer in which axillary lymph node metastasis is absent. Tissue microarrays were constructed. Following this, immunohistochemical staining was done for estrogen receptor (ER), progesterone receptor (PR), c-erbB2, and p53. The results were as follows: (1) expression of c-erbB-2 was correlated with other clinicopathologic factors (eg, patient's age, presence of menopause, tumor size, histologic and nuclear grade, and presence of hormone receptors such as ER and PR); and (2) expression of p53 was correlated with survival rate, patient's age, presence of menopause, and tumor size. However, these results were not statistically significant. In conclusion, our results indicate that expression of c-erbB-2 and p53 did not have any prognostic value in patients with early-stage breast cancer in which axillary lymph node metastasis is absent.     

The prognostic impact of hormone receptors and c-erbB-2 in pregnancy-associated breast cancer and their correlation with BRCA1 and cell cycle modulators

A population-based series of 122 patients with pregnancy-associated breast carcinomas was histologically revised and the relationship between hormone receptors, c-erbB-2, BRCA1, p27, cyclin E, and cyclin D1 was studied. The 5-year overall survival was 41%; 70% had tumor size >20 mm; 72% had metastasized to regional lymph nodes; 95% were histologic grade II or III; 66% and 75% were negative for estrogen and progesterone receptor, respectively; and c-erbB-2 expression was high (44%). BRCA1 expression was reduced in 33% of the cases. The expression of p27, cyclin D1, and cyclin E was low, 11%, 9%, and 16%, respectively. Cyclin D1 was positively associated with the hormone receptors (p< or =0.01). In multivariate analysis, lymph node status, progesterone receptor, and c-erbB-2 were significant prognostic factors. In subdividing the group according to lymph node status, c-erbB-2 and progesterone receptor retained a prognostic significance in the node positive group only. In conclusion, pregnancy-associated breast carcinomas are aggressive tumors, with low expression of hormone receptors, BRCA1, p27, and cyclin E and D1, and high expression of c-erbB-2.     

PROGNOSTIC SIGNIFICANCE OF THE CO-EXPRESSION OF p53 AND c-erbB-2 PROTEINS IN BREAST CANCER

The immunohistochemical expression of p53 and c-erbB-2 gene proteins was examined in a series of 130 breast adenocarcinomas. This study intended to investigate whether the frequency of the altered expression of the tumour suppressor gene p53 and the overexpression of the oncogene c-erbB-2 in breast cancer tissue cells correlated with other variables known to affect the biological behaviour of these tumours and the overall survival of the patients (median follow-up time: 6 years). The expression of p53 protein and c-erbB-2 gene product was evaluated immunohistochemically. Expression of p53 protein was detected in 30 (23 per cent) of the neoplasms examined, while 26 (20 per cent) out of the 130 cases demonstrated positive c-erbB-2 immunoreactivity. There was a statistically significant association between p53 protein expression and primary tumour size, lymph node involvement, and oestrogen receptor positivity. The incidence of c-erbB-2 positivity was significantly correlated with high tumour grade, axillary node invasion, large tumour size, and the absence of steroid receptors. p53 immuno-expression was clearly associated with c-erbB-2 protein overexpression. Concomitant p53 and c-erbB-2 positive immunolabelling, which emerged in 14 out of the 130 cases (10·7 per cent), was clearly associated with high grade, large size, positive nodal status, ductal infiltrating (NOS) histological type, and low values of progesterone receptors. Overall survival of patients was not significantly related to the immunoreactivity of either p53 or c-erbB-2 considered separately, whereas there was a clearly significant trend to worse overall prognosis in cancers with double p53/c-erbB-2 positive phenotype. The simultaneous immunodetection of p53/c-erbB-2 appears to have greater negative prognostic relevance than their separate expression.     

Remarkably high frequency of EGFR expression in breast carcinomas with squamous differentiation

The human epidermal growth factor receptor (EGFR) is reportedly overexpressed in 15-20% of breast carcinomas. EGFR overexpression is associated with reduced survival and is inversely correlated with expression of estrogen receptor (ER). This study assessed EGFR expression in breast carcinomas with squamous differentiation. The immunohistochemical (IHC) expression of EGFR was evaluated in 39 breast carcinomas with squamous differentiation (30 pure squamous, 6 adenosquamous, 3 carcinosarcomas) by use of the pharmDx assay (clone 2-18C9, DakoCytomation). Cases were considered positive if at least 10% of the cells showed 1+ positivity in the squamous component. Squamous differentiation was confirmed with IHC for CK5-6 (clone D5/16B4, DakoCytomation). ER, PR, and HER2 status as well as clinical information regarding treatment and outcome were correlated. As a control, a tissue microarray comprising 280 lymph node positive breast carcinomas was evaluated with the same EGFR assay. The 39 patients ranged in age from 33 to 77 years (mean 52). The tumors measured 1.3-30 cm (mean 4.8). Sentinel or full axillary lymph node dissection was performed in 28 patients. Fourteen patients had positive lymph nodes. At the time of initial diagnosis, 3 patients had distant metastasis. Follow-up was available for 16 patients (mean 45 months). Disease-free survival at 3 years was 70%. Among the 39 tumors 87% (34) were positive for EGFR (p<0.0001). Sixty-nine percent (27 of 39) showed >50% 2+ EGFR staining. EGFR-positive tumor cells (showing squamous morphology) were also found in 1 bone, 1 lung, and 8 of 11 lymph node metastases available for evaluation. All 11 lymph nodes showed squamous differentiation. All but 1 of the EGFR+ tumors examined were ER and PR negative. Six EGFR-positive tumors were HER2 positive. No statistically significant differences in HER2 status, size, lymph node status and disease-free survival were observed between EGFR+ and EGFR- cases, but the number of EGFR-negative tumors was quite small. Nine of 280 (3%) of lymph node-positive invasive carcinomas on the tissue microarray were EGFR+; review of the initial diagnostic slides failed to reveal squamous features in all but 1 of the 9 EGFR+ tumors. Breast carcinomas with squamous differentiation are a distinct subgroup of breast tumors with a very high frequency of EGFR positivity. Breast carcinomas of this type would be ideal candidates for a trial with EGFR inhibitors.     

Trisomy 15 in a case of pediatric hemangiopericytoma and review of the literature

HER2 (c-erbB-2) has been suggested to be a prognostic factor in a variety of human cancers including breast, gastric and ovarian cancers. This study is therefore designed to identify changes of HER2 in nasopharyngeal carcinoma (NPC), an epithelia-derived malignancy with strong racial and geographic distribution. Interphase FISH and immunohistochemical (IHC) staining were used to analyze the gene copy number and protein expression of HER2 in 45 cases of NPC from Guangzhou, Southern China, an area with the highest incidence of NPC in the world. Our results, however, found no significant alterations in gene copy number for HER2, although IHC staining detected expression of HER2 oncoprotein in 33% of the 45 NPC tumors. No correlation was observed between HER2 expression and sex, age and clinical outcome of the patients, T stage, lymph node status, site and histopathological grading of the tumors. These results cast doubt on the value of HER2 as a prognostic factor for NPC.     

乳腺癌的复发、转移与c-erbB-2、BCSG1等多指标相关性研究

 目的：探讨人表皮生长因子受体（c-erbB-2）、乳腺癌特异基因(BCSG1)等多指标在乳腺癌中的表达及其对复发、转移的影响以及其间的相关性。方法：采用免疫组化SP法检测随机抽取的随访5年临床病理资料完整的58例浸润性乳腺癌组织中的c-erbB-2、BCSG1以及雌激素受体（ER）、孕激素受体（PR）、微血管计数（MVD）、血管内皮生长因子（VEGF）、淋巴管内皮生长因子（VEGF-C）、淋巴管内皮生长因子受体（FLT-4）、淋巴管计数（LVD）蛋白的表达情况，结合临床、病理形态学资料分析多项指标对复发、转移的影响。结果：c-erbB-2、BCSG1、VEGF-C、LVD蛋白在乳腺癌组织中的阳性表达率分别为25.9%、62.1%、36.2%、32.8%；4指标表达在伴淋巴结转移组明显高于无转移组（P<0.05）；在复发、转移组其表达率同样显著高于无复发、转移组（P<0.05），且MVD在复发、转移组也增高（P<0.05）。结论：c-erbB-2、BCSG1、VEGF-C、LVD蛋白与患者的复发、转移密切相关，乳腺癌c-erbB-2、BCSG1蛋白在乳腺癌中的表达呈正相关，其中，BCSG1蛋白表达的灵敏性高，可尝试作为预测乳腺癌预后的指标。     

The prognostic significance of c-erbB-2 and p53 protein expressions in gastric carcinoma--a multivariate analysis of prognostic factors.

152 curative gastrectomy specimens from patients with gastric carcinoma were examined in an attempt to assess the prognostic value of c-erbB-2 and mutant p53 protein expressions. The labeled streptavidin-biotin method was applied to routinely fixed and paraffin-embedded tissue sections, using the polyclonal and monoclonal antibodies against the c-erbB-2 protein and the mutant form p53 protein, respectively. In this examination, staining of c-erbB-2 protein was found in 9.2% of these carcinomas. The c-erbB-2 stained tumors were significantly associated with the tumors whose diameters were smaller than 5cm, and were more likely to be associated with serosal invasion and nodal involvement than the unstained ones. However, there was little association between staining of c-erbB-2 protein and clinicopathologic findings such as age, sex, location, histology, gross type, lymph node status, depth of invasion, and stage. The survival analysis of 104 patients with stage III gastric carcinoma revealed no significant association between c-erbB-2 staining status and survival duration. The 5-year survival rates of the c-erbB-2 positive group and its negative group were 21% and 28%, respectively. Positive p53 protein expression was observed in 46% of 152 carcinomas. There was no significant association between p53 expression and parameters such as age, sex, location, histology, gross type, and size. The p53 stained tumors were more likely to be associated with lymph node metastasis, serosal invasion than p53 unstained ones; but this did not reach significance. The 5-year survival rates of the p53 positive group and counter part group were 27% and 31%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Type 1 protein tyrosine kinases in Chinese breast carcinomas: a clinicopathologic study

Immunostaining for epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3, c-erbB-4, ER, and PR was performed in 107 cases of primary breast carcinomas from Anyang, China. The expression rates of EGFR, c-erbB-2, c-erbB-3 and c-erbB-4 in this series were 43.9%, 36%, 27%, and 45.8%, respectively, and a stronger c-erbB-4 staining of "normal" glandular structures inside tumors and in the vicinity of tumor clusters was confirmed. Larger tumor size, lymph node metastases, and higher histologic grade in invasive ductal carcinomas were shown to be statistically valuable negative prognostic factors, and c-erbB-2 expression was also weakly associated with a poor prognosis no matter what the nodal status. The expressions of c-erbB-4 and ER in invasive ductal carcinomas were inversely associated with histologic grade of the tumors. Associations between the expression of c-erbB-4 and ER (p = 0.001) and the expression of ER and PR study (p = 0.004) were found in the present study. No significant associations between the expressions of EGFR, c-erbB-3, c-erbB-4, ER, and PR and overall survival were detected. The expression of c-erbB-4 in the node negative group was, however, associated with a better prognosis, indicating a different role of c-erbB-4 protein in breast tumor development than other EGFR family members have. Int J Surg Pathol 9(3):177-187, 2001     

Are Breast Cancer Molecular Classes Predictive of Survival in Patients with Long Follow-Up?

In this study we investigate the clinical outcomes of 305 breast cancer (BC) patients, aged 55 years or younger, with long follow-up and according to intrinsic subtypes. The cohort included 151 lymph node negative (LN−) and 154 lymph node positive (LN+) patients. Luminal A tumors were mainly LN−, well differentiated, and of stage I; among them AR was an indicator of good prognosis. Luminal B and HER2 positive nonluminal cancers showed higher tumor grade and nodal metastases as well as higher proliferation status and stage. Among luminal tumors, those PR positive and vimentin negative showed a longer survival. HER2-positive nonluminal and TN patients showed a poorer outcome, with BC-specific death mostly occurring within 5 and 10 years. Only luminal tumor patients underwent BC death over 10 years. When patients were divided in to LN− and LN+ no differences in survival were observed in the luminal subgroups. LN− patients have good survival even after 20 years of follow-up (about 75%), while for LN+ patients survival at 20 years (around 40%) was comparable to HER2-positive nonluminal and TN groups. In conclusion, in our experience ER-positive breast tumors are better divided by classical clinical stage than molecular classification, and they need longer clinical follow-up especially in cases with lymph node involvement.     

c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma

AIMS: The c-erbB-2 and c-Met proto-oncogenes are important for tumour invasiveness and metastasis in many types of malignant tumours. Previous studies have indicated that these proteins are associated with carcinogenesis in intrahepatic cholangiocarcinoma. In this study, we examined c-erbB-2 and c-Met expression by immunohistochemistry in hepatolithiasis, intrahepatic cholangiocarcinoma and metastatic lymph node, in order to clarify whether these proteins play a role in carcinogenesis and tumour metastasis in intrahepatic cholangiocarcinoma. METHODS AND RESULTS: In hepatolithiasis, the staining for c-erbB-2 was positive in 14 of the 23 (61%) cases, while staining for c-Met was positive in eight of the 23 (35%) cases. In intrahepatic cholangiocarcinoma, staining for c-erbB-2 was positive in 45 of the 81 (55%) cases, while staining for c-Met was positive in 28 (35%) cases. The positivity of c-Met staining in intrahepatic cholangiocarcinoma was significantly higher in the differentiated type of cholangiocarcinoma than in the undifferentiated type. In addition, c-Met-positive staining had an inverted correlation with tumour size, the presence of perineural invasion and the presence of lymph node metastasis. c-Met staining had a significantly higher positivity in cases at an early stage of intrahepatic cholangiocarcinoma. In contrast, the positivity of c-erbB-2 staining in intrahepatic cholangiocarcinoma was significantly higher in cases with lymph node metastasis than in cases without. In metastatic lymph nodes, the staining for c-erbB-2 was positive in 20 of the 25 (80%) cases, while staining for c-Met was positive in six of the 25 (24%) cases. There was no difference in survival between c-erbB-2-positive and negative patients. However, the patients with c-Met-positive tumours had a significantly longer survival than those with c-Met-negative tumours in the medium survival term. The multivariate analysis showed the presence of lymph node metastasis, lymphatic permeation and histological differentiation to be independent prognostic factors. CONCLUSION: These results indicate that increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma, while increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis.     

Over-expression of c-erbB-2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women

AIM: We aimed to investigate the immunohistochemical expression of c-erbB-2 in invasive breast carcinoma in Asian women and its correlations with clinicopathological parameters and nuclear morphometry. Patients were followed up for disease relapse and overall survival, and the data were reviewed in conjunction with c-erbB-2 over-expression. METHODS: Paraffin sections from 321 invasive breast cancers were immunohistochemically stained with anti-human c-erbB-2 antibody using the streptavidin-biotin technique. RESULTS: c-erbB-2 was over-expressed in 110 (34.3%) cases, with an inverse correlation with oestrogen receptor (ER) and progesterone receptor (PR) status (p=0.0001) and a positive correlation with histological grade (p=0.017). Nuclear morphometry in 96 cases revealed rounder nuclei in c-erbB-2 negative tumours (p=0.0322) when compared with c-erbB-2 positive tumours. Among c-erbB-2 positive cases, malignant cells of histological grade 3 tumours revealed larger nuclear area and perimeter than grade 1 and 2 cases (p=0.0095, p=0.03, respectively) while increasing tumour size correlated with greater nuclear perimeter (p=0.046). c-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (p=0.0166) and for subsets of node positive, histological grade 1 and 2, and ER positive tumours, and in women aged over 50 years (p=0.0047, p=0.0367, p=0.0092, p=0.0096, respectively). CONCLUSIONS: c-erbB-2 was independently prognostic when histological grade, nodal and ER status were considered. Our results show that c-erbB-2 over-expression correlates with poor histological grade and negative ER/PR status, and predicts poor overall survival in Asian women with breast cancer.     

Triple negative breast cancer: adjuvant chemotherapy effect on survival

PurposeThe purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.Material/MethodsThe study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated.ResultsThe overall survival of breast cancer patients was 97.0% (95% CI 90.9–99.0), 84.9% (95% CI 76.1–90.6) and 66.5% (95% CI 55.5–75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patient's age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients’ age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant.ConclusionPatients who had lymph node status N2–3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.     

Immunohistochemical cathepsin-D expression in breast cancer: correlation with established pathological parameters and survival

Breast cancer is an increasingly important cause of illness and death among women. In recent years, several novel prognostic determinants of breast cancer have been identified, including Cathepsin-D (CD) protein. CD protein expression was analyzed immunohistochemically (IHC) in tumor specimens (315 patients) of infiltrating ductal breast carcinoma. These patients also had axillary lymph node sampling. Overexpression of CD was observed in 39% of the tumors. IHC results were compared with the histological grade. Seventy nine percent (n = 95; 79%) tumor positivity was seen in grade II tumors, followed by grade I (n = 13; 11%) and grade III tumors (n = 12; 10%). Axillary lymph node metastasis had no significant correlation with CD positivity (p > 0.05). Bone metastases were significantly correlated with CD positivity (p < 0.05). CD positivity showed no significant correlation with disease-free and overall survival (p > 0.05). At a median follow-up of 48 (4 years) months in CD-positive patients, overall survival was 3.17 years, and disease-free survival 2.67 years. The overall survival of CD-negative tumor patients was 3.50 years, and disease-free survival was 2.93 years. We conclude that in comparison with cytosol-based quantitative studies, CD expression is not a good prognostic marker when, as in all ICH studies, only the expression in the tumor is considered.     

多项生物指标在乳腺癌中的表达及其关系与预后

目的 探讨多项生物学指标c-erbB-2,PCNA,P53,EGFR,nm23,ER,PR在乳腺癌中的表达与临床乳腺癌预后的关系及这些指标间的相互关系。方法 应用免疫组织化学方法对87例乳腺癌组织切片c-erbB-2,PCNA,P53,EGFR,nm23,ER,PR的表达进行检测。结果 乳腺癌远处转移率与腋淋巴结转移数目有关，c-erbB-2阳性率与肿瘤大小，临床分期正相关，PCNA阳性率与肿瘤大小，腋淋巴结转移数目正相关，P53与肿瘤大小正相关，c-erbB-2与PCNA，P53，EGFR，PR相关，P53与PR相关，ER与PR相关。结论 肿瘤大小，腋淋巴结转移数目，临床分期，c-erbB-2,PCNA,P53,PR等多指标联合应用有助于提高对乳腺癌预后评价的正确性。