Prognostic relevance of three histological grading methods in breast cancer.

Histological grading is an important parameter for the risk assessment in patients with breast cancer. However, up to now differing grading methods are used which have not been compared with respect to their prognostic significance. In the present study the prognostic significance of three different methods of histological grading (Elston, Contesso, Helpap) was determined in a sample of 292 patients. Furthermore, results obtained in needle biopsies were compared with those obtained in surgical resection specimens in 31 cases. The mitotic counts and the Contesso method were performed on two microscopes with different field areas (0.238 mm2 and 0.345 mm2). Univariate and multivariate analysis revealed that all three histological grading methods had a high prognostic value concerning overall survival (OS) and disease-free survival (DFS). Using univariate and multivariate analysis the Elston method performed best to determine OS and DFS (p<0.0001 and p<0.001). The field area of the microscope had a minor influence on the mitotic count and on the results of the Contesso method. The histological grading was reliable in needle biopsies: the best agreement to grading obtained in the definitive surgical specimen was achieved with the Elston method (kappa statistic 0.727). As a conclusion, we could show that determination of the histological grade is an important prognostic factor in breast cancer with the Elston method giving the best results. Also, we could demonstrate that histological grading in needle biopsies is reliable enough to allow a preoperative risk estimation.     

Invasive lobular breast cancer: subtypes and outcome

Invasive lobular carcinoma (ILC) is the most common "special type" of breast cancer. Although conflicting literature data are available on the outcome of ILC, recently reported data indicate that ILC carries a poorer prognosis if compared to invasive ductal carcinomas. We evaluated clinical and biological features of 981 consecutive patients with pT1-3, pN1-3 M0 ILC. Median follow-up was 7.4 years for survival. A total of 541 patients were classified as classic (55.8%), 146 alveolar (14.9%), 145 mixed non-classic (14.8%), 104 solid (10.6%), and 38 trabecular (3.9%). A statistically significant difference in the outcome was observed at multivariate analysis for patients with solid (HR 2.44, 95% CI 1.39-4.29 for OS; HR 1.92, 95% CI 1.29-2.88 for DFS) and mixed non-classic (HR 1.99, 95% CI 1.12-3.53 for OS) versus patients with classical ILC. A statistically significant difference in the risk of distant metastases was observed at multivariate analysis for patients with Luminal B (HR 2.56, 95% CI 1.38-4.76), HER2 positive (HR 7.80, 95% CI 1.55-39.3), and triple negative (HR 7.61, 95% CI 2.63-22.1) subtypes versus patients with Luminal A ILC. Age ≥70 years, tumor size and degree of nodal involvement were additional independent predictors of reduced overall survival. The outcome of ILC significantly correlated with histological and immunohistochemically defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.     

Observer variation in histological grading of breast cancer

A multicentre study was conducted to assess the degree of agreement between pathologists grading breast tumours using the WHO criteria. Satisfactory correlation of grades was found to occur with observer variation of 21.9% on 874 tumours.     

Prognostic value of the histological grading of cancer of the kidney

The data of morphologic examination of 83 cases of renal carcinoma were used for grading tumor malignancy (grades I--III). The classification is based on such quantitative parameters as nucleus-cytoplasm and nucleolus-nucleus ratios, percentage of nucleolus-containing nuclei, and size and DNA content of the nucleus. The grading system proved to be of prognostic value and easy to reproduce.     

Invasive breast cancer following ductal and lobular carcinoma in situ of the breast

We considered the risk of subsequent invasive breast cancer in a population-based series of 579 carcinomas in situ (CIS) of the breast (482 ductal, 88 lobular) registered between 1977 and 2002 in the Swiss Canton of Vaud. A total of 55 cases of invasive breast cancer were observed vs. 12.3 expected, corresponding to a standardized incidence ratio (SIR) of 4.5 (95% confidence interval [CI], 3.4-5.8). The SIR was 4.6 after ductal and 4.2 after lobular CIS, was similar with passing time since CIS diagnosis, but was higher (SIR = 5.5) for women aged <55 years. At 20 years following CIS, the cumulative risk of invasive breast cancer was 26%, similar for lobular and for ductal CIS. The incidence of invasive breast cancer following CIS showed no consistent pattern of trends with age, all rates in subsequent age groups ranging between 10 and 18 in 1,000. This is compatible with the occurrence of a single mutational event in a population of susceptible women.     

Does routine grading of invasive lobular cancer of the breast have the same prognostic significance as for ductal cancers?

AIM: The routine tumour grading of invasive ductal carcinoma of the breast has been shown to be a robust determinant of outcome but pathologists have been reluctant to grade lobular cancers. The aim of this study was to determine the prognostic significance of the routine reporting of lobular grade. METHODS: All patients with invasive lobular carcinoma (ILC) treated between 1981 and 1996 were reviewed. Patients with ILC which had been graded were included in the study. These cases were matched with two control patients with invasive ductal carcinoma (IDC) who were operated on in the same year and were closest to the patients in age. Recurrence-free survival was compared with grade for ILC cases and IDC controls using life-table analysis. Similar comparisons were made with the Nottingham Prognostic Index (NPI) between the different prognostic groups. RESULTS: Of 139 cases with ILC, 33 were excluded from the study because 24 were ungraded, five had advanced disease and four had mixed tumours. The mean length of follow-up for ILC cases was 75 months vs 70 months for IDC controls. Recurrence rates for grade I were 10% ILC vs 24% IDC, for grade II 32%vs 32% and for grade III 33%vs 49%. The reported grades for ILC and IDC both showed the expected trend for an increased recurrence rate with more severe tumour grade, but this was only significant for IDC grade II vs grade III (P<0.02) on life-table analysis; only 6% of lobular cancers were reported as grade III. However, there was significant separation of the survival curves when NPI was compared for both lobular and ductal cancers. CONCLUSION: The routine reporting of tumour grade for ILC did not show significant difference in outcome between grade I and grade II, and very few tumours were rated grade III. The validity of grading lobular cancer of the breast requires further evaluation.     

Prognostic significance of cathepsin-D in patients with breast cancer.

The expression of the protease cathepsin-D has been evaluated using an immunohistochemical technique with a polyclonal antibody in paraffin-embedded tissue from 359 patients treated between the years 1975-1981 for Stage I and II breast cancer. One hundred and twenty seven patients (35%) have strongly positive, granular staining, 138 (38%) are intermediately stained in the cytoplasm, and in 94 (26%) no staining is observed. There is a strong positive association between expression of cathepsin-D and the presence of tumour in axillary lymph nodes (P < 0.006). Expression of the protease is associated with significantly poorer survival of patients in univariate analysis (P = 0.025); however, this is not independent of other tumour variables.     

Problems in histological grading of malignancy and its clinical significance in patients with operable Breast Cancer

Although the histological grading of malignancy in patients with operable breast cancer, typically consisting of three factors: tubular formation, mitotic counts, and nuclear atypia, plays an important role in identifying patients at high risk of recurrence, the most effective combination of factors is still not completely clear. In assessing prognosis, the problems of clinical application of the grade of malignancy are not only related to the assemblage of the factors employed, but also to the heterogeneity within the tumor and interobserver variations. In a review of the correlation between the histological grading system for malignancy in operable breast cancer patients and the recurrence rate, only the grade of nuclear atypia statistically correlated with the rate of recurrence. Furthermore, a grading system consisting of mitotic counts and nuclear atypia was more significantly correlated to the risk of recurrence than was the system based on the three factors described above. Concerning the heterogeneity of histologic features within the primary tumor, a system based on the grade of mitotic counts or nuclear atypia showed a high degree of heterogeneity, but a system based on the grade of tubular formation showed low heterogeneity and bimodal distribution.     

Prognostic significance of young age in breast cancer

BACKGROUND: Breast carcinoma is relatively uncommon in younger women and whether or not young age at diagnosis is an adverse prognostic factor in this disease has been controversial. Our aim in this report is to determine whether the histopathologic features and outcome in young and old are different, and whether age is a prognostic factor for relapse. METHODS: A retrospective study of consecutive 281 stage I or II breast carcinoma patients who had modified radical mastectomy was carried out. The patients with a median follow-up period of 45 months were divided two groups according to their ages. The histopathological features and survival of Group 1 and Group 2 were compared with each other. Univariate and multivariate prognostic factor analysis for relapse were carried out. RESULTS: The patients in Group 1 (younger than 35 years of age) had the worst histopathological features related to the prognosis than those in Group 2 and the difference between the two groups was statistically significant. Whereas the rates of 5-year overall survival were 65% in Group 1 and 98% in Group 2 (P < 0.05), the rates of 5-year relapse-free survival were 40% and 80%, respectively (P < 0.05). In univariate analysis of all patients, pathologic tumour size, pathologic axillary status, number of metastatic lymph nodes, pathologic stage, age, lymphatic vascular invasion were statistically significant factors associated with relapse. Multivariate analysis demonstrated that number of metastatic nodes (risk ratio RR:4.3 in more than three nodes) and age (RR:3.6 in Group 1) were the most important independent prognostic factors for relapse. In the patients without axillary involvement, both of univariate and multivariate analysis revealed that pathologic tumour size (RR:5.1 in pT(2)) and age (RR:4 in Group 1) were the independent prognosticators for relapse. CONCLUSIONS: Young patients with breast cancer had the worst histopathological features and the worst survival than their older counterparts. Age was an independent significant prognostic factor for relapse.     

乳腺癌孕酮受体对预后的影响

Estrogen and progesterone receptors (ER and PR) were detected in 400 women with primary breast cancer from 1979 to 1986. Cytosols showing saturable binding of 10 fmol/mg protein or more were taken as positive for ER and PR. The positive rate was 55.5% and 42.8%, respectively in this series. PR negative patients had higher risk of early recurrence than PR positive patients according to the highly significant difference between the two disease-free survival curves (P less than 0.01). The relative risk of recurrence in the PR negative group was 3.2 times higher than PR positive group (P less than 0.01). Simple ER positive or ER negative did not provide any relevant information for predicting the disease-free survival in this present series. Thirty months after mastectomy, 32.2% of the patients with PR negative tumors had recurrent disease as compared with the PR positive group (10.2%) (p less than 0.01). The recurrent rate was negatively correlated with tumor PR concentration. The prognostic value of PR status with respect to clinical stage, menopausal status and axillary node involvement is discussed. It is concluded that the PR content of breast cancer is an important predictor of prognosis and will help us to formulate treatment plan for the patients.     

Prognostic significance of calcium-sensing receptor in breast cancer

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that is involved in tumor suppression of cancers. However, its role in breast cancer remains largely unknown. The aim of the study was to investigate the expression of CaSR in breast cancers and to evaluate its prognostic significance. We found that the protein levels of CaSR were significantly reduced in cancer lesion compared with its paired non-tumor tissues. By analyzing the expression of CaSR in a 148 cases of breast cancer tissue microarray (TMA) by immunohistochemistry, we found that patients with lower expression of CaSR were significantly associated with poor overall survival, cause-specific survival, and distant metastasis-free survival. The Cox multivariate analysis showed that CaSR was an independent prognostic significance for both overall survival and cause-specific survival of breast cancer patients. Our data confirmed the tumor suppressor role of CaSR and suggested that CaSR is an independent prognostic indicator of breast cancer.     

Vascular grading of angiogenesis: prognostic significance in breast cancer

The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P < 0.0001), node-negative patients (P < 0.0001) and node-positive patients (P < 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P < 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer.     

Prognostic significance of grading in lung adenocarcinoma

BACKGROUND:

Although grading has prognostic significance for many tumor types, a prognostically significant grading system for lung adenocarcinoma has not yet been established. The aim of this study was to evaluate histologic characteristics included in tumor grading systems, establish optimal cutoff values that have the strongest association with overall survival, and develop a grading system incorporating the histopathologic characteristics that the authors found to have prognostic significance in patients with lung adenocarcinoma.

METHODS:

The authors studied lung adenocarcinomas from 85 consecutive patients, and evaluated the percentage of solid pattern (as a reflection of tumor architecture), the degree of cytologic atypia, and the mitotic count.

RESULTS:

In univariate analysis, overall survival was associated significantly with sex (P = .045), age (P = .0008), tumor status (P < .0001), lymph node status (P = .02), solid pattern (P = .046), and cytologic atypia (P = .01), but not with mitotic count (P = .26). On the basis of optimal cutoff values, the authors found that a solid pattern ≥90% and severe cytologic atypia were the best discriminators of worse outcome. A grading score, computed as the sum of the architecture score and cytologic atypia score (2 = well differentiated, 3 = moderately differentiated, 4 = poorly differentiated), was a significant predictor of overall survival in univariate analysis (median overall survival times, 72.4, 39.5, and 8.7 months for well, moderately, and poorly differentiated adenocarcinoma, respectively; P = .0001). Moreover, grading was an independent predictor of survival in multivariate analysis (P = .002).

CONCLUSIONS:

The authors describe a grading system that incorporates the percentage of solid pattern and degree of the cytologic atypia that is an independent predictor of survival in patients with lung adenocarcinoma. Cancer 2010. © 2009 American Cancer Society.     

Invasive lobular carcinoma of the male breast: a case report.

A case of lobular carcinoma in a male breast is described. Because the structure of the male breast does not have lobules and acini, lobular carcinoma cases are seen infrequently. The pathological diagnosis was invasive lobular carcinoma of the breast. The karyotype of the patient revealed a 46 XY/46 XY, dmin (double minutes) chromosomal structure. Although 28% of the examined metaphases showed 46 XY, 1-5 dmin, the others were normal. We reviewed the English literature and found 20 reported cases of lobular carcinoma of the male breast. Our case represents lobular carcinoma in a proven genotypic male patient showing no exogenous or endogenous estrogens.     

Prognostic significance of scoring system based on histological heterogeneity of invasive ductal carcinoma for node-negative breast cancer patients

This study aimed to determine the prognostic significance of histological scoring system based on heterogeneity of invasive ductal carcinoma, for node-negative breast cancer patients. We studied 108 patients of node-negative invasive ductal carcinoma with invasive tumor >5 mm. Histological score of each patient was evaluated based on histological subtype of invasive ductal carcinoma and pattern of its heterogeneity. Score of each subtype was defined as follows; papillotubular carcinoma: score 1, solid-tubular carcinoma: score 2 and scirrhous carcinoma: score 3. The existence of histological heterogeneity was examined, and corresponding score was doubled in a pure case and scores of two dominant subtypes were summed in a composite case. Overall survival curves defined by sores were drawn by Kaplan-Meier method and the difference in survival rate was evaluated by log-rank test. The most significant difference of overall survival was recognized between low score group (scores 2, 3 and 4) and high score group (scores 5 and 6) (p<0.001). In addition, multivariate analysis confirmed that only histological score was an independent prognostic factor. These results suggested that assessment of histological heterogeneity of invasive ductal carcinoma could serve as independent potent prognostic factor for node-negative invasive ductal carcinoma of the breast, and this method might be useful to decide indication of postoperative adjuvant chemotherapy.     

Morphometrical malignancy grading is a valuable prognostic factor in invasive ductal breast cancer

The aim of the present study is to augment the prognostic power of breast cancer grading by elaboration of quantitative histopathological methods. We focus on the recently introduced morphometrical grading system in which the three grading sub-features of the WHO grading system are evaluated with the help of computerised nuclear morphometry, and quantitative methods for assessing mitotic activity and tubular differentiation. The prognostic value of the morphometrical grading system is now confirmed in a material of 159 cases of invasive ductal breast cancer. In the current material the morphometrical grading system very efficiently predicted the prognosis of breast cancer by dividing the patients into favourable (grade I), intermediate (grade II), and unfavourable (grade III) outcome (P<0.0001). The morphometrical grading system was especially efficient in identifying patients with the most unfavourable outcome. In our material the morphometrical grade III was associated with a 5.4-fold risk of breast cancer death. In light of the present results, the morphometrical grading can be applied to clinical use as an aid in treatment decisions of patients with invasive ductal breast cancer.     

Prognostic significance of minichromosome maintenance proteins in breast cancer

A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim to investigate the prognostic significance of these proteins in breast cancer. We studied the expression of MCMs in various datasets and the associations of the expression with clinicopathological parameters. When considered alone, high level MCM4 overexpression was only weakly associated with shorter survival in the combined breast cancer patient cohort (n = 1441, Hazard Ratio = 1.31; 95% Confidence Interval = 1.11-1.55; p = 0.001). On the other hand, when we studied all six components of the MCM complex, we found that overexpression of all MCMs was strongly associated with shorter survival in the same cohort (n = 1441, Hazard Ratio = 1.75; 95% Confidence Interval = 1.31-2.34; p < 0.001), suggesting these MCM proteins may cooperate to promote breast cancer progression. Indeed, their expressions were significantly correlated with each other in these cohorts. In addition, we found that increasing number of overexpressed MCMs was associated with negative ER status as well as treatment response. Together, our findings are reproducible in seven independent breast cancer cohorts, with 1441 patients, and suggest that MCM profiling could potentially be used to predict response to treatment and prognosis in breast cancer patients.