Dietary fat in relation to prognostic indicators in breast cancer

The relation of diet, especially fat intake, to recognized prognostic indicators for breast cancer was investigated in 666 women with a newly diagnosed infiltrating breast carcinoma. Diet during the year preceding diagnosis was assessed by interview using a food frequency questionnaire covering the intake of 114 food items. Prognostic indicators included axillary node involvement at diagnosis, estrogen receptor status, and selected histologic features of the primary tumor such as nuclear grade, histologic grade, tubule formation, mitotic activity, and nuclear size of tumor cells. After adjustment for total energy intake, age, body weight, and tumor size at diagnosis, an increase in saturated fat intake was related to an increased frequency of node involvement at diagnosis among postmenopausal patients. In contrast, an elevation in polyunsaturated fat intake was related to a reduction of the percentage of patients with positive nodes at diagnosis. This relation was observed among both premenopausal and postmenopausal patients. Dietary fat was not related to the estrogen receptor status of tumors. No association was found between dietary habits and histologic features of the primary tumor. These data suggest that dietary fat may have an effect on the growth or spread of breast cancer during the preclinical phase of the disease and that this effect may vary according to the type of fat considered.     

Bcl-2 protein expression in breast cancer in relation to established prognostic factors and other clinicopathological variables*

BACKGROUND:: Bcl-2 inhibits most kinds of programmed cell death and providesa selective survival advantage to various cell types. Bcl-2is physiologically expressed in ductal epi-thelia of the normalbreast. The biological significance of Bcl-2 (over)expressionfor the development and progression of breast cancer has stillto be evaluated. PATIENTS AND METHODS:: A series of 133 primary breast cancers was investigated forexpression of the Bcl-2 protein by immunohistochemistry of paraffin-embeddedtissue sections. Results were correlated with other variablesof established or presumed predictive value. RESULTS:: A significant positive correlation was observed between Bcl-2expression and positivity for estrogen and progesterone receptors(p < 0.001). High proliferative activity as assessed by Ki-67staining correlated inversely with Bcl-2 expression (p <0.001). Bcl-2 immunostaining was not related to positivity forc-erbB-1. It was negatively associated with overexpression ofc-erbB-2 (p = 0.04), whereas a strong positive correlation wasfound with expression of c-erbB-3 (p = 0.01). There was a significantinverse correlation between histological grading and immunoreactivityfor Bcl-2 (p < 0.001). No tumors tended to be Bcl-2 positive,but differences were not statistically significant.Background:Bcl-2 inhibits most kinds of programmed cell death and providesa selective survival advantage to various cell types. Bcl-2is physiologically expressed in ductal epi-thelia of the normalbreast. The biological significance of Bcl-2 (over)expressionfor the development and progression of breast cancer has stilto be evaluated. PATIENTS AND METHODS:: A series of 133 primary breast cancers was investigated forexpression of the Bcl-2 protein by immunohistochemistry of paraffin-embeddedtissue sections. Results were correlated with other variablesof established or presumed predictive value. RESULTS:: A significant positive correlation was observed between Bcl-2expression and positivity for estrogen and progesterone receptors(p < 0.001). High proliferative activity as assessed by Ki-67staining correlated inversely with Bcl-2 expression (p <0.001). Bcl-2 immunostaining was not related to positivity forc-erbB-1. It was negatively associated with overexpression ofc-erbB-2 (p = 0.04), whereas a strong positive correlation wasfound with expression of c-erbB-3 (p — 0.01). There wasa significant inverse correlation between histological gradingand immunoreactivity for Bcl-2 (p < 0.001). No tumors tendedto be Bcl-2 positive, but differences were not statisticallysignificant. CONCLUSION:: Bcl-2 was detected predominantly in differentiated tumors. Expressionwas associated with other favorable histopathological featuresand predictors of positive clinical outcome. Loss of Bcl-2 expressionseems to be linked to loss of hormonal regulatability, increaseddifferentiation and deregulated proliferation. Bcl-2, breast cancer, immunohistochemistry, prognostic factors     

Elastosis in relation to prognosis in primary breast carcinoma

The content of elastic tissue has been evaluated in 171 primary breast carcinomas. Of the tumors, 35% had no or very little elastic tissue in the malignant areas, 42% presented with medium elastosis, and 22% had gross elastosis. The occurrence of elastin has been related to different prognostic factors. An increasing amount of elastin was found with increasing amounts of estrogen receptor (p = 0.0003), while there was only a slight correlation to the progesterone receptor content. Furthermore, the highly differentiated tumors contained more elastin in their tumor tissue than the poorly differentiated tumors (p = 0.003), and parous women had significantly more elastin than nonparous women (p = 0.02). The presence of elastin was not, however, of any demonstrable prognostic significance.     

Molecular prognostic indicators in breast cancer.

Here we review a panel of oncogene products, proteases and markers of proliferation that have shown potential as prognostic indicators in primary breast cancer. The relative merits of specific genetic mutations as well as alterations at the protein level are discussed. Finally an assessment is made of the transfer of knowledge from the laboratory to the bed-side.     

Histologic prognostic indicators in hepatocellular carcinoma.

Survival and histologic features were studied in 80 patients with proven hepatocellular carcinoma (HCC). The overall survival was 50% at 3.5 weeks with a statistically significant drop in mortality rate after 8.5 weeks. Patients with diffuse clear-cell pattern, focal clear-cell pattern, and no clear cells in their tumors had a 50% survival rate at 14 weeks, 6 weeks, and 3 weeks respectively; the differences in survival rates were statistically significant between any pair (p less than 0.001). No correlation was found between survival and (1) cytologic differentiation, (2) histologic architecture, (3) degree of pleomorphism, or (4) presence of bile production, proteinaceous secretion, giant cells, or cytoplasmic hyaline bodies. Eosinophilic HCC with lamellar fibrosis was not observed in any of our materials. We concluded that the presence of clear cells was the only histologic feature of prognostic significance in our patients.     

Correlation of oncoprotein 18/stathmin expression in human breast cancer with established prognostic factors

Oncoprotein 18/stathmin (Op18) is a conserved cytosolic phosphoprotein that regulates microtubule dynamics. The microtubule destabilizing activity is regulated by phosphorylation, mediated by both growth factor stimulated- and cell-cycle regulating kinases. The protein is highly expressed in a variety of human malignancies. In human breast carcinoma, Op18 has previously been shown to be up-regulated in a subset of the tumours, however, no correlation with clinicopathologic characteristics has been reported so far. In the present study we have examined Op18 protein expression by quantitative Western blot analysis in a panel of 151 semi-consecutive breast carcinoma samples. Op18 levels were negatively correlated with oestrogen receptor (OR) expression and positively correlated with a high fraction of aneuploid cells, proliferation measured by proliferating cell nuclear antigen (PCNA) expression, tumour size and histopathologic grade. Taken together, and in contrast to what has been previously reported, the present study shows that high Op18 expression correlates with general predictive factors and is not restricted to a specific sub-group of breast carcinoma.     

An evaluation of the usefulness of primary tumour expression of MCA and CA15-3 as prognostic indicators in breast carcinoma.

CA15-3 antigen and mucin-like carcinoma associated antigen (MCA) show potential as clinically useful serum markers of breast carcinoma. Recently, immunohistochemical versions of these monoclonal antibodies have become available but few data are available as to their clinical usefulness. The aims of this study were (i) to assess CA15-3 and MCA expression by primary breast tumours and to correlate tumour immunoreactivity with tumour behaviour, and (ii) to investigate the relationship between immunohistological staining and oestrogen receptor (ER) status. Pathological material from 39 stage 1 (node free) breast carcinoma patients was assessed. The mean age was 51.3 (range 34-70) years, 19 were premenopausal and the mean duration of follow-up was 3.6 years (range 0.8-14 years). In each case two further sections were stained with antisera to the CA15-3 and MCA antigens. Staining of primary tumour was achieved in 38 cases. Low (less than 30% tumour cell staining) and intermediate (30-60% of cells staining) grade immunoreactivity with both monoclonals correlated with significantly shorter disease free intervals (P less than 0.05). Neither monoclonal can predict ER status. We conclude that the use of monoclonal antibodies to CA15-3 and MCA in staining primary breast carcinoma tumours and their axillary nodes may be a significant (P less than 0.05) prognostic indicator of future tumour behaviour and that this requires further evaluation.     

Influence of delay to diagnosis on prognostic indicators of screen-detected breast carcinoma

BACKGROUND: Although delay to diagnosis after a breast screening abnormality causes anxiety, its effect on prognosis is unknown. METHODS: Using pooled data from five Canadian organized breast cancer screening programs, the authors used unconditional logistic regression to evaluate the effect of delay to diagnosis on prognostic indicators among 4465 women with invasive breast carcinoma diagnosed in the ipsilateral breast within 3 years of an abnormal screen performed during 1990-1996. RESULTS: Women with high-suspicion screens (n = 1569) compared with those without (n = 2896) were more promptly investigated (median days from screen to diagnosis, 31 vs. 47; P < or = 0.0001), had larger tumors (79.4% vs. 55.9% > 10 mm; P < or = 0.0001), and were more likely to be lymph node positive (33.9% vs. 17.3%; P < or = 0.0001). For delays beyond > 12 to < or = 20 weeks, a linear trend of increased tumor size and lymph node positivity began to emerge. Controlling for suspicion, the authors found that odds ratios for tumor size greater than 10 mm were 0.9 (95% CI, 0.66-1.17), 1.2 (95% confidence interval [CI], 0.88-1.56), 1.5 (95% CI, 1.05-2.16), and 2.1 (95% CI, 1.15-3.86) for delays of > 12 to < or = 20, > 20 to < or = 52, > 52 to < or = 104, and > 104 < or = 156 weeks, respectively (p(trend) < or = 0.0001), compared with delays of > 4 to < or = 12 weeks. Similarly, odds ratios for lymph node metastasis were 1.0 (95% CI, 0.67-1.42), 1.2 (95% CI, 0.84-1.69), 2.2 (95% CI, 1.48-3.15), and 3.2 (95% CI, 1.84-5.55) for the same time intervals (p(trend) = 0.0033). CONCLUSIONS: The authors' findings suggest that delays to diagnosis of asymptomatic breast carcinoma of 6 to 12 months are associated with progression of breast carcinoma as measured by increasing risk of lymph node metastases and larger tumor size. A policy of early recall rather than biopsy for low suspicion mammographic abnormalities may introduce delays of this magnitude. The tendency to more expediently investigate women with high-suspicion, worse prognosis screens (suspicion bias) obscures whether delays shorter than 20 weeks also worsen prognostic indicators. Suspicion bias should be considered when interpreting the effect of delay on prognosis.     

Lymphatic vessel density as prognostic factor in breast carcinoma: relation to clinicopathologic parameters

Angiogenesis and lymphangiogenesis are essential for breast cancer growth and progression. This study aimed at investigating lymphatic microvessel density (LVD) and microvessel density (MVD) as prognostic markers in breast carcinoma. Forty breast carcinomas were immunostained for D2-40, CD31 and VEGF. Median lymphatic and blood microvessel densities, as well as VEGF expression, were related to each other and to clinicopathologic parameters including lymph node (LN) status. The efficacy of haematoxylin and eosin (H&E) in detecting lymphatic vessel invasion (LVI) compared to D2-40 immunostaining was also investigated. D2-40 stained normal lymphatic endothelium and myoepithelial cells, but with different staining patterns. D2-40 LVD related significantly to CD31 counts (r=0.470; p=0.002), and LN metastasis (Mann-Whitney U=101.500; p=0.043); however, it did not relate to age, tumor grade, tumor size or LVI. D2-40 identified LVI in 3 more cases (7.5%) than those detected by H&E. VEGF was expressed in 85%of cases, and was significantly related to CD31 and D2-40 counts (p=0.033 and 0.007, respectively). In conclusion, D2-40 LVD showed a significant association with LN metastasis, and can be considered to segregate patients with positive from those with negative LNs. D2-40 enhances the detection of LVI relative to H&E staining reflecting a potential for lymphatic metastatic spread and possible poor prognosis.     

新疆维吾尔族女性乳腺癌C-erbB-2和nm23表达和预后的关系

目的:探讨C-erbB-2、nm23在新疆维吾尔族女性乳腺癌的表达与临床病理因素的关系。方法采用S-P免疫组化方法,检测58例维吾尔族女性乳腺癌石蜡包埋组织和30例乳腺增生病变中C-erbB-2、nm23的表达情况。结果:58例维吾尔族女性乳腺癌组织中C-erbB-2、nm23蛋白阳性表达率分别为56.90%和70.70%,而在乳腺增生组织中的阳性表达率分别为13.30%和90.00%,与癌组织间存在显著差异(P<0.05)。C-erbB-2表达与临床病理特征之间无明显相关(P>0.05),nm23与临床分期、ER状态有关(P<0.05),而与肿瘤大小、腋淋巴结状态、病理类型、患者年龄、月经状况及PR状态无关。C-erbB-2和nm23的蛋白表达无相关(P>0.05)。结论:nm23低表达与维吾尔族女性乳腺癌的侵袭、转移及预后有关,可作为预测其临床预后的分子指标。     

Soluble and nuclear oestrogen receptor status in human breast cancer in relation to prognosis.

The relationship between oestrogen receptor (RE) content of primary breast cancer and subsequent prognosis was examined with regard to nodal status. It was found that, within a particular nodal group, patients with tumours containing fully functional RE experienced a longer disease-free interval than those with RE- disease. An earlier observation that RE- primary disease gave rise to distant metastases as first site of recurrence more frequently than did RE+ disease, was not sustained. However, patients with RE+ primary disease had a much reduced chance of dying from cancer within a 3-year period.     

C-erbB-2 protein and neuroendocrine expression in breast carcinomas.

90 primary breast carcinomas and 18 metastases were immunostained for c-erbB-2 protein and neuron specific enolase. 30 tumours were c-erbB-2 negative and NSE positive, 23 tumours were NSE negative and c-erbB-2 positive. 1 tumour expressed focal immunoreactivity for both markers. 54 of the 108 tumours (50%) did not express either marker. Hormone immunoreactivity was present in single cells and in small groups of cells in 18 of the 31 NSE positive tumours. Bombesin, neurotensin and prealbumin were present in 4 cases each, followed by beta-endorphin and VIP in 3 cases each, leu-enkephalin in 2 cases and gastrin, serotonin, substance P, glucagon and somatostatin in 1 case each. None of 10 NSE negative breast carcinomas were comprised of cells expressing immunoreactivity for hormones. By immunoelectron microscopic examination the c-erbB-2 protein was shown to be present on the cell membrane, on smooth areas, microvilli and in coated pits. Immunoreactivity was also expressed in vesicles in cytoplasm and along rough endoplasmic reticulum. The study shows that c-erbB-2 protein expression and neuroendocrine activity are present in different tumour cell populations. This supports the hypothesis that the presence of c-erbB-2 protein, indicating an elevated cellular tyrosine kinase activity with stimulation of growth, intracellular Ca++, and phosphatidylinositol derivates, means that the same cell does not need regulation of the same factors by stimulation of peptide hormone receptors. Thus the production of autocrine and paracrine factors is switched off.     

C-erbB-2、ER和PR在乳腺癌中的表达与预后意义

目的了解乳腺癌C-erbB-2、ER和PR的表达与预后的关系。方法应用免疫组化方法检测乳腺癌C-erbB-2、ER和PR蛋白表达。结果乳腺癌淋巴结转移组C-erbB-2的阳性表达高于未转移组,ER和PR的阳性表达低于未转移组;C-erbB-2阳性表达在I级、II级和III级之间呈明显上升趋势。结论ER、PR阴性病人伴随着较高的C-erbB-2阳性表达,在乳腺癌中预后较差     

IGFBP-3 gene expression and estrogen receptor status in human breast carcinoma.

Insulin-like growth factors (IGF) I and II are potent mitogens for breast carcinoma proliferation. IGF-mediated proliferative activity can be markedly enhanced by the presence of specific IGF-binding proteins (IGFBPs). IGFBP-3 has been shown to enhance IGF-mediated growth in a number of systems. Studies have demonstrated IGFBP-3 secretion only in estrogen receptor (ER)-negative breast carcinoma cell lines while IGFBP-3 could not be detected in media conditioned by ER-positive cell lines. We investigated whether a relationship exists between ER status and IGFBP-3 mRNA expression in human breast carcinoma biopsy specimens. We have detected IGFBP-3 mRNA in breast carcinoma tissue obtained from patients utilizing in situ hybridization. Quantitation of IGFBP-3 mRNA levels was performed utilizing image cytometry. There was a significantly higher expression of IGFBP-3 mRNA in ER-negative breast carcinoma specimens when compared to the ER-positive specimens. Whether this higher expression of IGFBP-3 mRNA and presumed secretion of IGFBP-3 by ER-negative tumors play a role in the rapid proliferation and poor prognosis of these tumors remains to be determined.     

Elevated expression of cyclooxygenase-2 in breast cancer and ductal carcinoma in situ has no correlation with established prognostic markers

BACKGROUND AND OBJECTIVES: Elevated expression of cyclooxygenase-2 (COX-2) has been established to be a feature of breast cancer. There has been inconsistency in the literature regarding the precise significance of this-some studies have found no clinicopathological relevance at all, whilst others have concluded COX-2 expression is an important biomarker in invasive disease and pre-cancerous lesions, correlating with poor prognostic features. We studied COX-2 expression in invasive ductal cancer (IDC) specimens and ductal carcinoma in situ (DCIS) in order to clarify these issues. METHOD: Archival specimens of IDC and DCIS (n = 39) were stained with a polyclonal antibody to COX-2. Results were correlated with recognised clinicopathological parameters. RESULTS: COX-2 expression occurred in 36.7% of IDCs and 54.5% of DCIS lesions. There was no correlation between increased expression and any clinicopathological features. COX-2 expression did not occur in adjacent non-cancerous tissue (ANCT). CONCLUSION: We have confirmed that COX-2 expression does occur in invasive cancers, in DCIS, and is not associated with established prognostic markers. The presence of COX-2 expression in DCIS and invasive cancers has positive implications for the future prevention and treatment of breast cancer with COX-2 inhibitors. A large proportion of tumours are, however, COX-2 negative and may be poor candidates for COX-2 suppression.     

Heat-shock-protein-27 (hsp27) expression in ovarian carcinoma: relation in response to chemotherapy and prognosis.

Heat-shock protein 27 (hsp27) is one of the small heat-shock proteins. Its expression in ovarian- and breast-cancer cell lines has been associated with resistance to cisplatin and doxorubicin. In addition, hsp27 expression appears to facilitate cellular growth, differentiation and motility. In several human carcinomas, hsp27 expression might also be related to worse prognosis. The aim of this study was to evaluate the prognostic value of hsp27 expression in patients with ovarian carcinoma in relation to their response to chemotherapy and overall survival. Hsp27 expression was assessed by immunohistochemistry in 77 patients with ovarian carcinoma stage IC-IV. All patients received cisplatin- and doxorubicin-based chemotherapy and had long-term follow-up. In 30 patients, paired tumour samples were available, obtained before and after chemotherapy. Hsp27 immunostaining was positive in 86% of patients before and in 72% of patients after chemotherapy. Hsp27 expression was not related to any clinicopathologic factor, including previously determined p53 expression. Univariate analysis showed that, in stage-III and -IV patients, younger age, no residual tumour after first laparotomy, < or = 1 litre ascites, response to first-line chemotherapy and absence of hsp27 expression were associated with longer median progression-free survival. However, in multivariate analysis, only age, ascites and response to chemotherapy retained independent prognostic value.     

环磷酰胺联合强的松建立人乳腺癌小鼠移植模型

  目的   将人乳腺癌细胞接种于具有正常免疫功能但受抑制状态的小鼠,以期建立乳腺癌小鼠模型。   方法   将40只雌性BALB/c随机平均分成4组,按环磷酰胺和强的松用量多少分为对照组、低剂量组、中剂量组、高剂量组。将人乳腺癌细胞接种于小鼠背部,观察小鼠成瘤时间、成瘤率、肿瘤的影像、病理学表现及其重要内脏器官转移情况等。   结果   高剂量组成瘤率高,成瘤时间早,且内脏器官转移多,小鼠死亡率高。中剂量组成瘤率较低,成瘤时间较晚,内脏器官转移少,小鼠死亡率低。对照组和低剂量组未见成瘤和小鼠死亡。   结论   本实验成功用环磷酰胺联合强的松在免疫正常的小鼠中建立人乳腺癌小鼠移植瘤模型,较好的模仿乳腺癌在免疫正常的机体里的发生、发展过程。