Monique Trojani

Reproducibility of a histopathologic grading system for adult soft tissue sarcoma

Tumor grade has been proposed as an essential factor in the staging of patients with soft tissue sarcomas. In a previous study, a histopathologic grading system using the evaluation of tumor differentiation, mitosis count, and tumor necrosis was described. The current study was conducted to test its reproducibility. The pathologic sections of 25 soft tissue sarcomas were submitted to a study group composed of 15 pathologists who had not been involved in the development of the grading system. The results were compared with those of a panel group. The crude proportion in agreement observed between the study group and the panel group was 81% for the evaluation of tumor necrosis, 74% for tumor differentiation, and 73% for the mitosis count. The crude proportion in agreement for the tumor grade was 75%, which was significantly better than the crude agreement rate of 61% for the diagnosis of histologic type (P = 0.001). A kappa statistical analysis, to check the possibility of chance‐related concordance, showed a proportion in agreement of 68%. A two‐way variance analysis showed that the homogeneity of the evaluation of tumor grade is impaired by tumor‐related and observer‐related factors. However, an improvement may be obtained by better training of pathologists. We conclude that the tumor grading system developed inside the French Federation of Cancer Centers, although perfectible, already provides reliable prognostic information and its use in prospective clinical studies may provide more information about its clinical usefulness. Cancer 58:306–309, 1986.

Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi

Primary chemotherapy in operable breast invasive carcinoma enables tumour reduction and conservative surgery. In order to search for one or more biological factors capable of predicting tumour behaviour under primary chemotherapy, and subsequent patient survival, an immunohistochemical study was performed with specific antibodies to p53, c-erbB-2 (Her-2/neu), Mib1 (antiKi-67), pS2, GST pi, oestrogen receptors (ERs) and progesterone receptors (PRs). Core biopsies, obtained before primary chemotherapy, were available from a series of 128 breast invasive carcinomas treated between January 1985 and April 1989, with a median follow-up of 93.3 months. Univariate statistical analysis showed that negative ER detection by immunohistochemistry (IHC) was highly correlated with chemosensitivity (P = 0.001). A high percentage of Mib1-positive tumour cells (> 40%), as well as initial tumour size less than 4 cm, were also correlated with tumour responsiveness to chemotherapy (P = 0.009 and P = 0.03). By multivariate analysis IHC-ER, Mib1 and initial tumour size were independent predictors, the last parameter being the most important. Concerning subsequent patient survival, c-erbB-2 overexpression, as detected by IHC, was significant with respect to overall survival (OS) (P = 0.0006), disease-free interval (DFI) (P = 0.03) and metastasis-free interval (MFI) (P = 0.008) by univariate analysis. Furthermore, c-erbB-2 was the major independent prognostic factor for OS and MFI by multivariate analysis.

The prognostic value of c-erbB2 in primary breast carcinomas: A study on 942 cases

SummaryTo assess the practical prognostic value of c-erbB2, we performed a study on 942 invasive ductal carcinomas treated with primary surgery between 1980 and 1986 in our center. We evaluated its expression by immunohistochemistry in paraffin-embedded tissue using a polyclonal antipeptide antibody. Of 942 tumors, 229 (24%) showed a positive membrane staining. We observed a significant association between c-erbB2 and Scarff-Bloom-Richardson grading (p < 0.0001) and a negative correlation between c-erbB2 and both estrogen and progesterone receptors (p < 0.0001). In our analysis, with respect to overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS), c-erbB2 was statistically significant (p ≤ 0.0001) for the whole group and the node-positive subgroup. In multivariate analysis, c-erbB2 appeared to be an independant variable for RFS and MFS in the node-negative group. However, in our hands, c-erbB2 had a poor prognostic value in comparison with the classical prognostic variables such as histological grade, nodal status (N), hormonal receptor status (estrogen and progesterone receptors), and tumor size, and it did not supersede the classical parameters.

Histopathologic grading in spindle cell soft tissue sarcomas

Tumor grade is currently the most important factor in the staging of patients with soft tissue sarcomas. In previous studies, a histopathologic grading system was described and its reproducibility was tested. The current study reports the value of this grading system in spindle cell sarcomas, which represent about one half of all adult soft tissue sarcomas, the precise identification of which is often difficult. One hundred twenty‐five such tumors were studied retrospectively. Malignant fibrous histiocytoma was the most frequent histologic type, followed by leiomyosarcoma, neurosarcoma, and fibrosarcoma. Tumor grade was correlated with the advent of metastases and survival, and was the main prognostic factor according to multifactorial analysis introducing clinical prognostic factors.

Prognostic value of p53 in breast invasive ductal carcinoma: an immunohistochemical study on 942 cases.

SummaryP53 immunohistochemical detection using DO7 antibody on 942 cases of previously untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9 months (89 to 160) was performed.Three hundred and three (32%) tumors were positive. All positive tumors were taken into account, positivity ranging from 1 to 100% of tumoral cells. The Chi square test showed significant negative correlation between p53 positivity and age (p = 0.01), estrogen receptor status (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant positive correlation with tumor grade according to the Scarff, Bloom and Richardson system (SBR Grade) (p < 0.0001). There was no significant association with tumor size or nodal status.Concerning the univariate analysis, in the whole group and node-positive group (n = 544) p53 positivity was highly significant for overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p = 0.0003). In the node-negative group (n = 398), p53 was significant with respect to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent prognostic parameter in the multivariate analysis in the whole group and the node-positive group, though of minor significance compared to axillary lymph node status, SBR grade, progesterone receptor status, and tumor size.

Prognostic significance of Ki‐67 and topoisomerase IIα expression in infiltrating ductal carcinoma of the breast

To evaluate the prognostic relevance of Ki‐67 and topoisomerase IIα expression in relation to tumor stage, grade, and hormone receptor content, 942 ductal infiltrating carcinomas of the breast were examined by means of the monoclonal antibodies Ki‐S11 (Ki‐67) and Ki‐S4 (topoisomerase IIα). pS2, c‐erbB2, and p53 were additionally considered as prognostic variables. The median follow‐up time was 149 months. Eight‐hundred‐and‐sixty‐three tumors reacted with Ki‐S11 and Ki‐S the labeling indices of the two antigens were closely associated (r=0.93). Both correlated positively with the tumor size, c‐erbB2, and p53 expression, and negatively with patient age, hormone receptor content, and pS2 immunostaining. In the univariate analysis, Ki‐S11 and Ki‐S4 scores, nodal status, tumor size, tumor grade, and progesterone receptor content strongly predicted both overall and metastasis‐free survival (p <0.00001). Estrogen receptor status, p53, and c‐erbB2 were of minor significance. Concerning overall survival, multivariate Cox regression analysis selected a Ki‐S4 score >25% (p < 0.00001) next to the nodal status, and before tumor size, progesterone receptor content, and patient age. Independent predictors of the occurrence of distant metastases were nodal status, Ki‐S4, tumor size, grade 1, and progesterone receptor negativity, in that order. The Ki‐S11 score was of independent prognostic significance only if examined as a continuous variable. We conclude that topoisomerase IIα expression as assessed by monoclonal antibody Ki‐S4 may add valuable information to current prognostic models for breast cancer. Its predictive value appears to be essentially related to the proliferative activity of tumor cells.

Low-grade follicular lymphomas: Analysis of prognosis in a series of 281 patients

From 1963 to 1988, 281 patients with newly diagnosed follicular lymphomas were treated and followed at the Foundation Bergonié. Distribution of stages was: 72 I, 61 II, 83 III and 65 IV. Within stage III, two subgroups were retrospectively defined: stages III1 (32 cases) included patients with less than 8 involved sites, only 1 or 2 above diaphragm, and no spleen or mediastinal enlargement. Stage III2 (51 cases) included the remaining stage III cases. Median follow-up was 9 years. Complete remission (CR) rate was 82%. 10-year overall survival (OS) and time to treatment failure (TTF) rates were, respectively 38% and 29.5%. 10-year time to relapse (TTR) rate was 36%. Statistical analyses showed concordant results with two main prognostic factors: age (less than 60/greater than 60) and stage (I to III1/III2 and IV). Age was the most important factor for OS analysis and stage for CR and TTR analysis. This leads to only three prognostic groups with different outcome. The first includes younger patients (less than 60 years) with limited stages (less than or equal to III1); the second, patients either older than 60 or with advanced stages; the last, elderly patients with advanced stages. CR rates of these three groups were, respectively 97%, 75% and 57%. 10-year OS were, respectively 73.5%, 27% and 0%; 10-year TTR were 54%, 22% and 0%. These results have lead to data which are easy to handle and which can help to establish a rationale for further prospective trials.

Application of the Van Nuys prognostic index in a retrospective series of 367 ductal carcinomas in situ of the breast examinated by serial macroscopic sectioning: Practical considerations

The Van Nuys prognostic index (VNPI) was thought to be useful for predicting response to radiotherapy and local recurrence of ductal carcinoma in situ (DCIS). We applied the VNPI under the conditions defined by Silverstein et al., in 367 retrospective DCIS entirely sectioned into serial macroscopic 2u2009mm slices (155 patients had radiotherapy, median follow-up 71 months). The percentage of positive blocks with DCIS was also estimated for each specimen with cut-offs at 30% and 60% to obtain three scores. One hundred and ninety five lesions had a low VNPI, 152 an intermediate VNPI, and 20 a high VNPI. There were 9% of local recurrences (half invasive, all in the group without radiotherapy) in the low VNPI group. The local recurrence rate increased with size (p=0.001), with reduction of distance to margins (p=0.05), with histologic grade (p=0.02), with percentage of positive blocks (p=0.0003) and with VNPI score (p=0.03). The percentage of positive blocks was the only independent predictor for local recurrence (p=0.0001).Conclusion: (1) The VNPI was a local recurrence rate predictor between the low and the intermediate groups but in our series the low VNPI group had a surprisingly high local recurrence rate. (2) Only prospective studies will assess the importance of margin width and the role of radiotherapy in maintaining local control. (3) Estimation of the percentage of positive blocks is simple, may be an alternative when measurement of DCIS is difficult and should be taken into account.

Transanal electroresection of small rectal cancer : A sole treatment ?

PURPOSE: Because abdominoperineal resection is associated with high morbidity and mortality, there is interest in local treatment of distal rectal carcinoma. Our technique of transanal electroresection ensures full-thickness tumor excision and complete histopathologic examination. METHODS: From July 1983 to July 1990, 227 patients underwent surgery. Criteria for cure were no extramural invasion (61 exclusions) and negative margins (34 exclusions). Six patients underwent postoperative radiotherapy and, therefore, were excluded. RESULTS: Among those included were 126 patients (66 men), who had a mean age of 68±11 (median, 68) years. Median tumor size was 35 mm. Distance from anal verge was less than 6 cm for 68 percent and 6–10 cm for 30 percent of patients. Deepest layer invaded was as follows: submucosa (T1), 35 percent; inner muscular layer (T2a), 42 percent; outer muscular layer (T2b), 23 percent. There was one postoperative death. Immediate postoperative course was uneventful for 94 percent of patients; at long-term, five cases of incontinence and two stenoses were noted (6 patients). Median follow-up was 88 (1–137) months. Global survival was 71 and 46 percent, and cancer-specific survival was 85 and 81 percent at 5 and 10 years, respectively. Of 35 patients (28 percent) with recurrence, 24 were treated. Global survival after recurrence was 72 and 50 percent at one and two years, respectively. The only pejorative prognostic factors isolated for survival or recurrence were mucinous contingent and intratumoral vascular invasion. CONCLUSION: Results of local treatment for rectal carcinoma in selected patients are favorable (5-year specific survival, 85 percent). Decisive prognostic factors are seldom isolated, but some patients would benefit from an adjuvant therapy.

Immunohistochemical determination of pS2 in invasive breast carcinomas: A study on 942 cases

SummaryTo assess the practical prognostic value of pS2, we evaluated its expression by immunohistochemistry in paraffin-embedded tissue from 942 previously untreated invasive ductal carcinomas (IDC) resected in our center between 1980 and 1986. Positive staining of tumor cells was found in 684 cases (73%), but most of the tumors contained only a small amount of positive cells. There was a negative correlation between pS2 and tumor size (p = 0.01) and histological grade (p < 0.0001), and a positive correlation between pS2 and hormonal receptor status (p < 0.001). With respect to overall survival, pS2 positivity was associated with a better prognosis for the whole group and the node-positive sub-group. However, in terms of relapse and metastasis, pS2 was not significant. Furthermore, in multivariate analysis including tumor size, nodal status, histological grade, ER status, PR status, chemotherapy, hormonal treatment, and pS2, the latter appears to be of no prognostic value.