Histological grade and other prognostic factors in relation to survival of patients with breast cancer.

Records of 3085 patients registered with breast cancer at the Mersey Regional Cancer Registry have been analysed to evaluate the relative importance of possible prognostic factors. In a subgroup of 1759 patients, clinical stage and histological grade are shown to be strongly related to survival after treatment. In addition histological grade is related to the distribution of times to death after treatment. The results of this and 3 other studies have implications for the design and analysis of clinical trials in the primary treatment of breast cancer.     

MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder: clinical significance and comparison with other prognostic factors

BACKGROUND: Staging and grading of transitional cell carcinoma of the bladder are generally viewed as indicators of prognosis and form the basis of therapy, but they do not predict outcome accurately. This study was designed to evaluate the value for predicting recurrence, progression, and survival of proliferation fraction in transitional cell carcinoma of the bladder determined by immunostaining of histopathologic specimens with the monoclonal antigen MIB-1. METHODS: In a prospectively followed group of 301 patients with transitional cell carcinoma of the bladder, formalin fixed tumor specimens were immunostained and the MIB-1 labeling index was determined. Crude survival, progression free survival, and recurrence free survival (for patients with Ta and T1 tumors) were assessed in univariate and multivariate analysis according to stage, grade, mitotic index of the tumor, and patient age. The median value of continuous variables was used as a cutoff point in statistical analysis. RESULTS: In univariate analysis there was a strong association between all included factors and crude survival, progression free survival, and recurrence free survival with a median follow-up period of 60 months. In multivariate analysis, crude survival and progression free survival were determined by stage (P = 0.0001) and age (P = 0.0001). Recurrence free survival for patients with Ta and T1 tumors was determined by MIB-1 labeling index (P = 0.0317), mitotic index (P = 0.0229), and age (P = 0.0001). CONCLUSIONS: MIB-1 immunostaining in transitional cell carcinoma of the bladder correlated well with grade, stage, and clinical outcome. In multivariate analysis, proliferation fraction had prognostic value in predicting recurrence free survival for patients with Ta and T1 tumors, whereas stage and age appeared to be predictors of progression free survival.     

Medullary thyroid carcinoma: multivariate analysis of prognostic factors influencing survival

Background Medullary thyroid carcinoma (MTC) is a rare development of thyroid cancer with a no negligible mortality rate. Our aim was to determine factors that predict outcome in patients with MTC. Methods We reviewed the records of all patients with MTC (n=56) who underwent treatment at our institution between January 1990 and December 2000. Univariate and multivariate analysis of clinicopathologic predictors of MTC outcome were performed to identify subsets of patients with different probabilities in terms of overall survival, local recurrence, and distant metastases. Results Multivariate analysis demonstrated that a statistically significant decrease in overall survival is associated with T4b tumours (p=0.06), the presence of distant metastases at the time of presentation (p=0.033), lymphatic invasion (p=0.099), and postoperative treatment (p=0.045). Conclusions The analysis of survival curves of patients with MTC shows that the occurrence of locoregional and distant metastases occurs preferentially within the first 5 years, which identifies this as a crucial period for follow-up. In this series of patients with MTC, the tumours classified as T4b, metastases at presentation, the presence of lymphovascular invasion, and postoperative treatment were the most important prognostic features. At present, there is no available beneficial adjuvant therapy. However, as the development of molecular therapy progresses, it should be tested in clinical trials with the purpose of achievement of novel targeted therapies for selected MTC patients with risk factors.     

Dietary factors and the survival of women with breast carcinoma.

BACKGROUND: Little is known regarding how specific dietary factors affect the survival of women with breast carcinoma. METHODS: Female registered nurses were followed with biennial questionnaires in a prospective cohort with 18 years of follow-up. Participants were women with breast carcinoma (n = 1982) diagnosed between 1976-1990 who completed a food frequency questionnaire after diagnosis. The main outcome measure was time to death from any cause. Analysis was made by multivariate Cox proportional hazards models. RESULTS: In multivariate analyses of diet after diagnosis, no apparent association was found between fat intake and mortality. The relative risk (and 95% confidence interval) of mortality comparing the highest with the lowest quintile of protein intake was 0.65 (0.47-0.88). There was no association between red meat and mortality. These associations were similar in analyses with breast carcinoma death as the outcome. CONCLUSIONS: No survival advantage was found for a low fat diet after a diagnosis of breast carcinoma. However, increased survival was observed among women eating more protein, but not red meat. The findings suggest that differences in diet may affect survival after a diagnosis of breast carcinoma and should be examined in greater detail.     

Relationship of ethnicity and other prognostic factors to breast cancer survival patterns in Hawaii

The survival experience of 2,956 invasive breast carcinoma cases identified among the 5 major ethnic groups in Hawaii between 1960 and 1979 was studied. The study population consisted of 1,174 Caucasian, 972 Japanese, 458 Hawaiian, 226 Chinese, and 126 Filipino women. A multivariate analysis based on the proportional hazards regression model revealed that after simultaneous adjustment for stage of disease, age, and socioeconomic status (SES), Filipino and Hawaiian patients had significantly poorer survival than Japanese and Caucasian patients. Hawaiian women also had a significantly poorer survival than Chinese women. Survival was higher in patients between the ages of 45 and 54 years compared to those younger or older, in patients with localized tumors compared to those with more advanced tumors, and in patients with middle or high SES compared to those with the low SES. Histology and marital status were not associated with survival. The possibility that other factors such as obesity, estrogen receptor status, treatment, and nutritional and hormonal status could explain the remaining observed racial differences in breast cancer survival is discussed.     

Female breast cancer in Gipuzkoa: prognostic factors and survival

Background  In Gipuzkoa, screening for breast cancer was initiated in 1997 and in this paper we present breast cancer characteristics and survival for women diagnosed during the pre-screening period. Methods  All cases diagnosed during 1995–1996 were included and the tumour characteristics were analysed. One-, five- and ten-year observed and relative survival (RS) were estimated overall, as well as by age and tumour characteristics. Multiple regression models were used to evaluate the effect of tumour characteristics on ten-year RS. Results  Six hundred and twenty-two cases with a mean age of 60.7±15 years were included. The mean follow-up was 7.5 years (max. 10) with a mortality of 40.5%. Ductal carcinoma accounted for 78% of all cases; almost 50% had good or moderate differentiation and 28% were positive for both hormone receptors studied. Nearly 80% of cases were diagnosed in stage I or II and breast-conserving surgery was employed more often than mastectomy. Age-standardised RS was 77% (95% CI 72.1-82.3) and 68% (95% CI 60.4–74.6), five and ten years after diagnosis respectively. The relative excess risk of death was significantly different only for age, stage and degree of differentiation. Discussion  This study shows an increase in survival compared to previous studies in the region. This could be explained by advances in diagnosis and treatment, as demonstrated by younger age and earlier stage at diagnosis and by the therapy profiles. Age and stage were shown to be major predictors of survival in our study and adjustment for the other factors had only limited effects on the risk of death for these two variables.     

Morphometric studies in intraductal breast carcinoma using computerized image analysis.

A morphometric study was performed using computerized image analysis on the histologic specimens of 26 patients with intraductal carcinoma of the breast and 26 normal control patients. A significant incidence of necrosis (56%) was observed in the breast ducts containing intraductal carcinoma. This was characterized by one or more areas of necrosis surrounded by a rim of viable tumor cells. The mean diameter of the ducts containing intraductal carcinoma was 349 microns compared with a mean diameter of 90 microns for the normal ducts. The mean diameter of the ducts containing necrosis was 470 microns compared with a mean diameter of 192 microns for the ducts containing a solid pattern of intraductal carcinoma. Central necrosis occurred in 94% of the ducts more than 180 microns in radius, whereas only 34% of the ducts less than 180 microns in size contained necrosis. The width of the viable neoplastic tissue was less than 180 microns in 91% of the ducts. These results are analogous to the findings of Thomlinson and Gray in human lung tumor cords and provide indirect evidence for the existence of a hypoxic compartment in intraductal carcinoma of the breast. This could be an explanation for the higher local failure rate after conservative surgery and irradiation for infiltrating cancers containing an extensive intraductal component.     

Cell proliferation measured by MIB1 and timing of surgery for breast cancer.

We have investigated the use of the antibody MIB1 as a proliferative and prognostic marker in breast cancer and whether changes in proliferative activity could account for differences in prognosis of premenopausal women operated on during different phases of the menstrual cycle. MIB1 expression was strongly correlated with S-phase fraction and histological grade. There was no difference in MIB1 scores between different phases of the menstrual cycle. Both MIB1 score and timing of surgery correlated significantly with duration of survival, while the two together were even stronger predictors of overall survival. Women with slowly proliferating tumours surgically removed in the luteal phase had a very good prognosis, whereas women with rapidly proliferating tumours excised at other times of the cycle had a worse prognosis.     

Long survival and prognostic factors in hepatocellular carcinoma

We studied survival and prognostic factors in all cases of hepatocellular carcinoma seen at a Midwestern teaching hospital from 1947 through 1986. Of the 70 cases, 56 were diagnosed during life and 14 at autopsy. There were 47 males and 23 females with age at diagnosis ranging from 14 to 88. Median survival for the 56 patients diagnosed during life was 106 days. Only 11 patients lived longer than one year. Two patients were long survivors and presumed cured, one living 27 years after diagnosis and surgical treatment and the other 19 years. Cox regression model showed young age at diagnosis and low stage of disease at diagnosis to be significant predictors of long survival. White patients survived nearly twice as long as black patients but the difference was not significant. Gender and year of diagnosis did not appear to be important determinants of survival. Pathologic material was still available for one of the two long survivors and the histology was that of fibrolamellar carcinoma of young adults.     

Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival

Background: Clearance of large molecules from the interstitialspace is an important function of lymphatics andis affected by local pathologic changes.Objective: To determine if the clearance rate ofinterstitially injected albumin is correlated to tumour characteristicsand outcome in women with invasive breast cancer.Method: In a consecutive series of women comingto biopsy for suspected breast cancer, technetium-tagged albuminwas injected into the tissue adjacent to thepalpable mass. The isotope disappearance rate was measuredover two hours. Also assessed were the maximumvessel density (MVD – using Factor VIII polyclonalantisera), the proliferation rate (using Ki-67 antisera), nodestatus, tumour size, histologic and nuclear grade, mitoticrate, and p53 and c-erbB-2 oncoproteins. All patientswere followed until relapse and for a minimumof 10 years.Results: In multivariate analysis, an association between relapse-freesurvival and isotope clearance rate was suggested (p= 0.024). The best outcome was seen inpatients with the least isotope clearance. Node status,size, histologic and nuclear grade, and mitotic ratecorrelated with survival. MVD did not correlate withsurvival and was inversely related to the isotopeclearance rate. Tumour proliferation rate, and the c-erbB-2and p53 oncoproteins did not relate to outcome.Conclusion: The role of lymphatics in breast canceris difficult to study. Measurement of interstitial clearancemay be a useful technique and could bea prognostic factor.     

淋巴结转移情况不同的乳腺浸润性导管癌病理预后因素对比分析--介绍体视学参数在乳腺浸润性导管癌预后中的应用

目的　对比分析淋巴结转移情况不同的乳腺浸润性导管癌病理预后因素。探讨其体视学参数对判断预后的价值。方法　根据体视学原理 ,采用模板法 ,测定淋巴结阳性 13 7例和阴性 2 0 6例病例的癌实质体积密度 (Vv)及癌巢的表面积密度 (Sv) ;以Bloom Richardson和Elston分级法进行组织学分级。比较淋巴结情况不同时Sv、Vv及组织学分级与预后的关系。结果　无论淋巴结情况及组织学分级如何 ,Sv与预后负相关 ,Vv与预后正相关。癌巢表面积密度Sv≤ 4.4患者 89.3 %生存 5年以上 ,称安全型 ,Sv >5 .5患者 82 .5 %死于 5年以内 ,称危险型。此外 ,Sv <1.8患者 ,均生存5年以上 ,Sv >9.4患者均死于 5年以内。淋巴结阳性组的Sv值高于阴性组 (P <0 .0 1)。此结果Sv正判率 (CA ) 89.2 6%、灵敏度 (SE) 0 .92 5 0、特异度 (SP) 0 .82 93。结论　癌肿生长方式的体视学参数 -Sv值可作为独立判断预后的指标。高Sv值与淋巴结转移关系密切 ,高Sv值同时淋巴结阳性是 5年内死亡的高危因素 ,而Vv、淋巴结转移、组织学分级是乳腺浸润性导管癌预后的相关因素     

Prognostic significance of cell proliferation in human neuroblastoma: comparison with other prognostic factors

Peripheral neuroblastic tumors (PNT), are heterogeneous neoplasms that include neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN) and present great biological heterogeneity. There are few reports analyzing PCNA and Ki-67 expression in PNT; however, controversy exists concerning the specificity of PCNA as a real proliferative marker. The objective of our study was to determine which of these cellular proliferation markers is more specific on cellular cycle and could contribute with more information on the cell cycle. We found that PCNA was expressed in NB unfavourable cases, with MYCN amplification and high mitosis-karyorrhexis-index (MKI). Whereas, Ki-67 showed statistical significance regarding cases unfavourable with intermediate and high MKI, aneuploid and stages 3 and 4. Survival showed that patients with tumor not expressing Ki-67 (MIB1) lived longer than those without PCNA (88.93 vs 74.05%). We conclude that Ki-67 expression permits reliable detection of the cellular proliferation neuroblastoma fraction and provides useful prognostic information when associated with other biological factors.     

Population-based analysis of prognostic factors and survival in familial melanoma.

PURPOSE: Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. PATIENTS AND METHODS: This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. RESULTS: Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). CONCLUSION: These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.     

CD24 expression is a new prognostic marker in breast cancer.

PURPOSE: CD24 is expressed in hematological malignancies as well as in a large variety of solid tumors including breast cancer. We aimed to evaluate CD24 protein expression in breast cancer and to correlate to clinicopathological data including patient survival. EXPERIMENTAL DESIGN: Primary breast carcinomas (201) with a mean clinical follow-up time of 53 months were immunostained using a monoclonal CD24 antibody (Ab-2, clone 24C02). The staining was evaluated as negative versus positive for statistical analysis. RESULTS: In invasive breast carcinomas, CD24 expression was observed in 84.6% of cases. In univariate survival analyses, a significant association of CD24 expression with shortened patient overall survival (5-year survival rate 91.9% versus 83.8%; P = 0.031; log rank test) and disease-free survival (5-year progression rate 88.3% versus 57.0%; P = 0.0008) was demonstrated. In multivariate analyses CD24, tumor grading and nodal status were significant prognostic parameters for shortened disease-free survival. CONCLUSIONS: Our data suggest that CD24 expression in primary breast cancer as detected by immunohistochemistry might be a new marker for a more aggressive breast cancer biology.     

Prostatic carcinoma: a multivariate analysis of prognostic factors.

Tissue specimens from 150 patients with localised prostatic carcinomas and 116 patients with prostatic carcinomas with distant metastases were analysed for histological grade (WHO and Gleason) and immunoreactivity for prostate acid phosphatase (PAP), prostate-specific antigen (PSA), neurone-specific enolase (NSE), p53 protein, c-erbB-2 protein, cytokeratins (AE1/AE3) and vimentin. After stratification for the presence or absence of distant metastases, multivariate regression analysis revealed that WHO grading was the most powerful independent prognosticator, followed by age and prostate acid phosphatase expression. There was a trend towards reduced survival with decreasing prostate-specific antigen reactivity. The Gleason system showed poor prognostic ability. The analysis predicted reduced survival in the presence of extensive neurone-specific enolase reactivity, mostly because of one case of small-cell carcinoma.     

Prospective multicenter comparison of proliferation and other prognostic factors in lymph node negative lobular invasive breast cancer

Evaluation of prognostic factors in lymph node negative (LNneg) invasive lobular cancers (ILCs). Prospective analysis of proliferation and other prognosticators in 121 LNneg ILCs (119 months median follow-up, range 19–181), without adjuvant chemotherapy. ILC subtype was assessed in accordance with WHO-2003 criteria. Immunohistochemical E-cadherin and estrogen receptor were used. With a median follow up time of 83 months (range 19–181), 30 of the 121 (25%) ILC patients developed distant metastases and 27 (22%) died. None of the cases classified as solid/pleomorphic lobular were E-cadherin or estrogen receptor positive, contrasting the other ILCs. The solid/alveolar ILCs (n = 17) had a worse survival (50%) than the other ILCs (n = 104; 83%, P < 0.0001). Mitotic activity index (MAI) (but not nuclear grade or tubule formation) was prognostic with a threshold 0–5 versus >5 (=MAI-5) (contrasting MAI < 10 vs. ≥10 in breast cancers in general; 85 and 54% survival, P < 0.0001). In multivariate analysis only subtype and MAI but none of the other characteristics had independent prognostic value. Histologic subtype and MAI have independent prognostic value in node negative invasive lobular cancers.