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The option to treat patients presenting with HER-2 overexpressed invasive breast carcinoma with Herceptin requires quantitative determination of the HER-2 status. The aim of this study was to retrospectively evaluate the HER-2 mRNA expression levels using quantitative real-time RT-PCR (Q-RT-PCR) in tissue samples from 44 primary breast carcinomas and compare the results with immunohistochemistry (IHC). To determine the cut-off for altered mRNA expression, a normalized HER-2 expression value was determined for 20 normal breast tissue RNAs. Gene expression was categorized into three groups: normal expression (mRNAs <3); moderate overexpression (3 < or = mRNAs < 10) and strong overexpression (mRNAs < or =10). More than 38% (17/44) displayed strong overexpression, 25% (11/44) moderate and 36.3% (16/44) normal expression. Compared to IHC, only 7/44 cases were slightly discordant: strong mRNA overexpression/2+ protein staining (1 case), moderate overexpression/ 1+ (3 cases) and moderate overexpression/3+ (3 cases). These results show a high concordance rate (84%) between Q-RT-PCR and IHC (p < 10(-4)). We conclude that Q-RT-PCR is a useful complementary method for determination of the HER-2 status.

Looking back to three decades of professional experience allows to evidence the dramatic changes of the role of the pathologist in breast cancer clinical management. Increasing means, fruitful exchanges within pathologists, and closer collaborations with other specialists have been key mediators of this evolution.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop practice guidelines according to the definitions of the Standards, Options and Recommendations project for the content of the anatomic and surgical pathology or cytopathology reports in field of oncology., Methods: Data were identified either by searching on Medline or via members of the expert groups personal references lists. When the guidelines were defined, the document was submitted to 49 independent reviewers, and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations for the composition of the anatomic and surgical pathology or cytopathology reports in oncology are 1/ The reports must contain the identification of the pathologist, of the patient and of the specimen, a gross description for the surgical specimen, eventually a microscopic description, the diagnosis, all the elements essential for establishing the prognosis and for the clinical care, and a conclusion. 2/ The reports could contain some comments. 3/ The reports must be brief, precise, clear, homogeneous and ideally standardised, in order to be comprehensible for all the clinicians and the pathologists.

Background: Cell proliferation is a major determinant of the biologic behavior of breast carcinoma. MIB-1 monoclonal antibody is a promising tool for determining cell proliferation on routine histologic material. The objectives of this study were to compare MIB-1 evaluation to other methods of measuring cell proliferation, with a view to refining the cutoff used to classify tumors with low and high proliferation rates in therapeutic trials., Methods: One hundred eighty-five invasive breast carcinomas were evaluated for cell proliferation by determining monoclonal antibody MIB-1 staining, histologic parameters (Scarff-Bloom-Richardson grade and mitotic index) on paraffin sections, S-phase fraction (SPF) by flow cytometry, and thymidine-kinase (TK) content of frozen samples., Results: There was a high correlation (P = 0.0001) between the percentage of MIB-1 positive tumor cells and SPF, TK, histologic grade, and the mitotic index. Multivariate analyses including MIB-1 at 5 different cutoffs (10%, 15%, 17% [median], 20%, 25%) and the other proliferative markers showed that the optimal MIB-1 cutoff was 25% and that the mitotic index was the proliferative variable that best discriminated between low and high MIB-1 samples. A MIB-1 cutoff of 25% adequately identified highly proliferative tumors. Conversely, with a MIB-1 cutoff of 10%, few tumors with low proliferation were misclassified., Conclusions: The choice of MIB-1 cutoff depends on the following clinical objective: if MIB-1 is used to exclude patients with slowly proliferating tumors from chemotherapeutic protocols, a cutoff of 10% will help to avoid overtreatment. In contrast, if MIB-1 is used to identify patients sensitive to chemotherapy protocols, it is preferable to set the cutoff at 25%. The MIB-1 index should be combined with some other routinely used proliferative markers, such as the mitotic index., (Copyright 2002 American Cancer Society.)

In Europe, patients who may benefit from Herceptin((R)) (an HER2 targeted drug) are currently selected by immunohistochemistry (IHC). Reliable detection of HER2 status is essential to the appropriate usage of Herceptin(R), because its specificity is limited to tumours overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma be optimized and reliable. This technical paper reviews the different steps of the IHC technique, the controls and, the rules for interpretation. The sensitivity of the IHC technique must be adjusted so as not to produce false negatives or false positives. As opposed to other methods, it can be carried out whatever the fixation conditions of the tissues. The interpretation of the immunostains also requires training; it is fraught with problems for intermediate positivities. The ideal score to evaluate HER2 status has not yet been defined. It will thus be necessary to report the percentage of stained cells, the intensity of the staining, and, in respect to Herceptin((R)) treatment, the HercepTest scoring system (recommended in the package insert). Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs). FISH should be used for complementary assessment of 2+ cases (on condition that they have not been fixed in Bouin's liquid) and for the calibration of the IHC technique.

We assessed the reliability of hormonal receptors (HR) by means of immunohistochemisty (IHC) on cell blocks obtained from diagnostic fine-needle cytopunctures in a group of 142 primary breast carcinoma. The results were compared to biochemical assessment (EIA) on their corresponding tissue samples (118 surgical specimens and 24 core needle biopsies). Percentage of stained nuclei and a score incorporating the proportion and the intensity of positive nuclei were evaluated. A two-group classification (cutoff 10% of stained nuclei) was used to define HR status. Highly positive tumors (>= 50% of stained nuclei) were also individualized. Regarding HR status, concordance rate between immunostaining and biochemical assessment was 86.6% for ER and 76.8% for PR. Major discrepancies were found in 6.3% and 15.5% of cases for ER and PR, respectively. A good correlation was also observed between quantitative values obtained by the two methods (r = 0.69 for ER and 0.60 for PR). Discrepancies were mainly related to weak positive staining, values close to the respective cutoffs and when biochemical evaluation was performed on core needle biopsies. We conclude that IHC on cell blocks prepared from fine-needle cytopuncture specimens of breast carcinomas is useful as a routine procedure for hormonal receptor determination especially when planning neoadjuvant treatment.

Before replacing enzyme immunoassay of estrogen and progesterone receptors by immunohistochemistry, results of both methods were compared on 437 samples obtained from breast cancer patients (342 primary breast carcinomas, 16 local recurrences, 49 biopsies, and 30 tumor specimens obtained after neoadjuvant treatment). Immunohistochemistry (IHC) results were first assessed semiquantitatively on the basis of the estimated proportion of positive tumor cells, and then quantitatively using the "quick score." Semiquantitative IHC hormone receptors results (positive > or = 10%) correlated well with enzyme immunoassay status (positive >15 fmol/mg protein) in 358 surgical samples (342 primary tumors and 16 recurrences), with overall concordance rates of 89.9% and 82.1%, respectively. Among the 100 discordant cases, a large intraductal carcinoma component was observed in 7 of 36 cases for estrogen receptor (ER) and 15 of 64 for progesterone receptor (PR). Thirty-five discordant cases also were observed near the cut-off values. Hormone receptor levels by enzyme immunoassay correlated strongly with the quantitative IHC "quick score." Whatever the method, hormone receptor status was associated with histologic grade (SBR) and tumor size, whereas age correlated strongly with ER positivity. Similar results were obtained for biopsy specimens and posttreatment samples. This comparison improved the reliability of the IHC technique, which is currently routinely used for ER and PR determination in the authors' institution.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993 is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for difficult diagnoses in surgical pathology or cytopathology in cancer patients., Methods: Data were identified by searching Medline and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 71 independent reviewers., Results: The main recommendations to prevent and reduce the number of difficult diagnoses in surgical pathology or cytopathology are: 1) The development of quality insurance programs with use of written procedures in each pathology laboratory (standard). 2) The knowledge of clinical data in order to explain surgical pathology or cytopathology results (standard). 3) The availability of complementary patient informations (radiologic data . . .) can be useful to explain surgical pathology or cytopathology results (option). The main recommendations to detect lesions associated with difficult diagnosis in surgical pathology or cytopathology are: 1) Tumor types known as potential difficult diagnosis in surgical pathology or cytopathology should be reviewed by a second pathologist. 2) The systematic second reviewing for every case is expensive but has to be done when the difficulty is know (sarcoma, lymphoma . . .) by experienced pathologists. The main recommendations to solve difficult diagnosis in surgical pathology or cytopathology are: 1) Block recuts, use of special techniques (immunocytohistochemistry and molecular biology), additional data from clinicians, second opinion by a local pathologist, or new specimen can be required for establishing the diagnosis (options). 2) Outside second opinion by expert pathologist has to be considered once the other steps did not allow to establish surgical or cytopathology diagnosis (recommendations, expert agreement).

The estrogen receptor (ER) status of breast tumors is used to identify patients who may respond to endocrine agents such as tamoxifen. However, ER status alone is not perfectly predictive, and there is a pressing need for more reliable markers of endocrine responsiveness. Here, we identified the well-known CGA gene (coding for the alpha subunit of glycoprotein hormones) as a new ERalpha-responsive gene in human breast cancer cells. We used a real-time quantitative reverse transcription-PCR assay to quantify CGA mRNA copy numbers in a large series of breast tumors. CGA overexpression (> 10 SD above the mean for normal breast tissues) was observed in 44 of 131 (33.6%) breast tumor RNAs, ranging from 20 to 16,500 times the level in normal breast tissues; the highest levels of CGA gene expression were close to those observed in placenta. Significant links were observed between CGA gene overexpression and Scarff-Bloom-Richardson histopathological grade I+II (P = 0.015), and progesterone (P = 0.0009) and estrogen (P < 10(-7)) receptor positivity, which suggested that CGA is a marker of low tumor aggressiveness. We observed CGA mRNA overexpression in 44 of 90 (48.9%) ERalpha-positive tumors and in none of the 41 ERalpha-negative tumors. Immunohistochemical studies demonstrated that human chorionic gonadotropin alpha protein was strictly limited to ERalpha-positive tumor cells. Overexpression of the CGA gene was not accompanied by overexpression of the CGB gene. Our results also suggest that CGA could be a more reliable marker than PS2 and PR for ERalpha functionality and, thus, for endocrine responsiveness. Moreover, the CGA marker has the added value of dichotomizing ERalpha-positive patients into two subgroups of similar size. Specific antibodies directed to secreted human chorionic gonadotropin alpha protein are commercially available, thus facilitating the future application of this marker to the clinical management of breast cancer.

Purpose: To identify most significant and therapeutically relevant prognostic factors in adults with localized primary synovial sarcomas (SS) and to confirm the usefulness of the French Federation of Cancer Centers (FNCLCC) grading system, the prognostic impact of which has been already proven in soft tissue sarcomas., Patients and Methods: Data on 128 patients with nonmetastatic SS collected from a cooperative database by the FNCLCC Sarcoma Group between 1980 and 1994 were studied retrospectively. Immunohistochemistry was performed at diagnosis in 77 cases (61%). The tumors were classified as biphasic (n = 45), monophasic fibrous (n = 72), and poorly differentiated (n = 10) subtypes. Histologic grade was determined according to the FNCLCC method, and vascular invasion was assessed in every case., Results: The 5-year disease-specific survival (DSS) rate for this series of patients with localized SS was 62.9% (+/- 9.6% [SD]) with a median follow-up time of 37 months (range, 8 to 141 months). In multivariate analysis, the adverse risk factors associated with decreased DSS were International Union Against Cancer/American Joint Committee on Cancer stage III/IVA disease, male sex, and truncal tumor locations. For metastasis-free survival (MFS), disease stage III/IVA, tumor necrosis, and monophasic subtypes were the major factors associated with a less favorable prognosis. Separately, when not using disease stage, tumor necrosis, and mitotic activity, histologic grade became the most significant prognostic factor for both DSS and MFS. In addition, larger tumors and older patients become associated with a significantly worse prognosis. Independent adverse risk factors for local recurrence-free survival included histologic grade 3 and truncal tumor location., Conclusion: These data confirm that not all SS present the same severe outcome. High-risk patients identified on the basis of these parameters may qualify for an aggressive treatment approach.

Synovial sarcoma (SS) is a relatively rare sarcoma, which may be confused with several other mesenchymal and nonmesenchymal lesions. It bears the t(X;18) (SYT;SSX) translocation, which seems to be specific for this tumor type and can be detected in paraffin-embedded tissue, using reverse transcriptase-polymerase chain reaction (RT-PCR). However, the specificity and sensitivity of this detection method have rarely been examined in a large series. Using RT-PCR, we examined 250 mesenchymal and nonmesenchymal, benign and malignant, paraffin-embedded lesions for the SS t(X;18) (SYT-SSX) translocation. PCR products were obtained from 221 tumors (88.5%). There were 135 non-SS tumors, 22 biphasic, and 64 monophasic spindle/round cell SS, of which 10 were cytogenetically confirmed as t(X;18)-positive. SYT-SSX gene fusion transcripts were detected in the SS tumor category only (100% specificity), including 100% of the biphasic SS and 86% of monophasic spindle/round cell SS. Nine tumors originally diagnosed as SS were t(X;18) (SYT-SSX)-negative. Following reassessment, only 3 of these tumors showed clinicopathologic, immunohistochemical, and/or ultrastructural features consistent with that diagnosis, thus raising the overall detection sensitivity to 96%. With regard to the potential adverse effect of the fixatives used, PCR products were obtained in 100%, 91.5%, 90.5%, and 0% of tumors fixed with AFA, buffered formalin, Holland Bouin, and conventional Bouin's fluid, respectively. This study shows that the detection of the SS t(X;18) (SYT-SSX) in paraffin-embedded tissue is feasible with a 100% specificity and an overall 96% sensitivity, provided non-Bouin's fluid fixation is used.

The aim of this study was to evaluate c-erbB-2 overexpression by means of a quantitative biochemical technique in 488 primary breast cancer patients with long-term follow-up (median, 10 years) and its relation to other biochemical prognostic factors (uPA, p53, and epidermal growth factor receptor) and adjuvant therapy. High levels of c-erbB-2 (>500 IU/mg protein) were associated with estrogen receptor (ER) and progesterone receptor negativity, high histoprognostic SBR grade and high levels of uPA and p53. Univariate analyses showed shorter metastasis-free survival (MFS) and overall survival (OS) in patients whose tumors overexpressed c-erbB-2 in the overall population, in subgroups defined by ER and uPA status, and in patients with positive pathological nodal status, SBR grade II, progesterone receptor, and p53-negative tumors. Patients with ER-positive, c-erbB-2-positive tumors had a shorter MFS and OS than those patients with c-erbB-2-negative tumors. No difference was observed between adjuvant-treated and untreated patients (chemotherapy and/or hormone therapy) in the c-erbB-2-negative subgroup. There was a trend toward a longer short-term MFS in c-erbB-2-positive patients treated with chemotherapy, whereas an opposite effect was observed with hormone therapy. Cox multivariate analyses showed that high levels of c-erbB-2 negatively influenced MFS in the overall population as well as in node-positive patients and in tamoxifen-treated patients, along with pN and uPA. Results for OS were comparable with those obtained for MFS. These results suggest that c-erbB-2 overexpression in breast cancer may be a better predictor of the response to tamoxifen than is ER status alone.

We assessed the reliability of prognostic biologic markers by means of immunohistochemistry on cell blocks obtained from diagnostic fine-needle cytopunctures of breast carcinomas and their lymph node metastases. Immunohistochemical studies of MIB-1 (Ki-67), estrogen receptors (ER), progesterone receptors (PR), p53, and c-erb-B-2 were performed in 55 cases of primary breast carcinoma on cell blocks (cytoblock technique) and on their corresponding tissue samples (46 mastectomy specimens and 9 Trucut biopsies) and in 38 cases on cell blocks from fine-needle cytopunctures of both the primary breast tumors and their concurrent lymph node metastases. Interobserver reproducibility ranged from 87 to 100%, depending on the marker. A good correlation was observed between immunostaining assessment on cell blocks and on the corresponding tumor tissues as follows: Ki-67 (85%), ER (96%), PR (82%), p53 (76%), and c-erb-B-2 (84%). An excellent correlation was observed between cell-block results for primary tumors and node metastases; however, a far higher percentage of Ki-67-positive nuclei was observed in the nodes than in the corresponding tumors in seven cases. All nodes corresponding to ER- or PR-negative tumors were also negative, whereas the nodes corresponding to two ER-positive and one PR-positive tumor were negative. Marked discrepancies were also noted with p53 in two cases and with c-erb-B-2 in two cases. Most discrepancies occurred with Trucut biopsies and with breast tumors that contained a large intraductal component. We conclude that cell blocks prepared from fine-needle cytopuncture specimens of breast carcinomas and their node metastases are useful when planning neoadjuvant treatment.

Within the Rubis 4th framework of European project is led a pilot experiment of tools and services for health professionals in prospect for the Aquitanian healthcare network. The sarcoma group of the FNCLCC (47 people) uses on its web site a multidisciplinary dialogue with a specific discussion forum. This service allows the anonymous publication of a imaging clinical case and to start a take care discussion. 87 cases were published in 13 months involving 261 answers from February 1999 to February 2000. A case is published every 4 days on average and the deadlines for replies regularly drop (15 days in February 1999 down 1.1 day in February 2000). The cases are published either for a diagnosis or treatment request (30%) or for the physical preparation of meeting or for the continuous medical training (70%). There are many advantages in comparison with the other possibilities of discussion: availability, autonomy of publication, cost, number of experts participating. These NTIC services will be developing within the regional healthcare oncology networks and are already tested by other regional groups (Lymphoma) considering the simplicity of use, management and training of the functionality.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop practice guidelines according to the definitions of the Standards, Options and Recommendations project for the content of the anatomic and surgical pathology or cytopathology reports in field of oncology., Methods: Data were identified either by searching on Medline or via members of the expert groups personal references lists. When the guidelines were defined, the document was submitted to 49 independent reviewers, and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations for the drafting of the anatomic and surgical pathology or cytopathology reports in oncology are: 1) The reports must contain the identification of the pathologist, of the patient and of the specimen, a gross description for the surgical specimen, eventually a microscopic description, the diagnosis, all the elements essential for establishing the prognosis and for the clinical care, and a conclusion. 2) The reports could contain some comments. 3) The reports must be brief, precise, clear, homogeneous and ideally standardised, in order to be comprehensible for all the clinicians and the pathologists.

A retrospective analysis of histological lesions adjacent to 67 invasive vulvar squamous cell carcinomas (SCC) was undertaken to analyse their nature, as well as their relationship to SCC. Patient age, clinical presentation and histological type of carcinoma, ISSVD classification of its adjacent lesions, disease-free and overall survival were reviewed. Severe undifferentiated vulvar intra-epithelial neoplasia (VIN3) was found in 19.4% of cases and vulvar lichen sclerosus (VLS) in 76.1% of cases. All VLS, except 2 cases, were associated with squamous cell hyperplasia (SCH), and a concomitant differentiated VIN was found in 76.6% of cases. Undifferentiated VIN3 was never associated with VLS. VLS was significantly associated with a keratinizing, well-differentiated SCC (98% of cases), while undifferentiated VIN3, was linked preferentially to 2 other types of SCC: in 77% of cases, a moderately-differentiated SCC with the same histological features as the so-called basaloid carcinoma and, in 23% of cases, a well-differentiated SCC with a variable extent of koilocytic atypia, similar to the so-called warty carcinoma. Carcinoma of the fourchette was more often associated with undifferentiated VIN3. Disease-free and overall survival were significantly better for carcinoma associated with undifferentiated VIN3 (p < 0.01 and p < 0.05, respectively). These findings suggest invasive vulvar SCC occurs on 2 distinct types of vulvar lesions: differentiated VIN and/or SCH associated with VLS and undifferentiated VIN3. Furthermore, the histological type of the carcinoma seems to differ according to adjacent lesions.

Background and Objectives: In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor., Methods: We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm., Results: In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors)., Conclusions: The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

Objective: To evaluate nuclear grading on fine needle cytopunctures of breast carcinoma, which is of special interest when neoadjuvant chemotherapy is planned., Study Design: In a prospective study, we compared cytologic grading, based on nuclear parameters (pleomorphism and mitosis), to modified Scarff-Bloom-Richardson histologic grading in 105 primary operable breast carcinomas. The results of these two nuclear grading systems were compared to Feulgen image analysis data from the corresponding cytologic samples., Results: The concordance rate between the two grading systems was 76%. Concordance between cytologic and histologic grading was observed more frequently in purely invasive carcinomas (85%) than in cases combining invasive and in situ components (56%). A highly significant relationship was observed between the two grading systems and indices of proliferative activity (S-phase fraction, proliferation index, 5c exceeding rate and endoreduplication rate), particularly in concordant grading. Furthermore, nuclear area correlated with the results of the two grading systems., Conclusion: Cytologic nuclear grading appeared to be a reliable tool for a large proportion of breast tumors. Despite difficulties related to tumor heterogeneity, which could be detected by careful cytologic examination, it is a useful alternative to histologic grading.

Angiosarcomas rarely develop within a peripheral nerve or a peripheral nerve sheath tumor. We describe an epithelioid angiosarcoma that arose in a benign schwannoma (neurilemoma) of the right thigh in a 65-year-old man who did not have von Recklinghausen's disease. Histologically, the resected tumor was a high-grade undifferentiated sarcoma that was predominantly arranged in solid sheets or nests and composed of epithelioid cells. The endothelial origin of the tumor was suggested by Factor VIII R-ag, Ulex europaeus-I, CD34, CD31, BNH9, and vimentin immunoreactivity, along with the ultrastructural evidence of occasional Weibel-Palade bodies. In this location, epithelioid angiosarcoma should be distinguished from malignant transformation of a schwannoma with epithelioid changes. This observation stresses the importance of immunohistochemical and ultrastructural analysis in the differential diagnosis of vascular tumors with features of epithelioid sarcoma.

Background: The purpose of this study was to determine the independent prognostic variables in a well documented subset of 216 patients with localized primary malignant fibrous histiocytomas (MFH)., Methods: Between the years 1980 and 1989, 216 patients with localized, primary (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC] Stage I-IVA) MFH were evaluated and treated in 10 participating centers of the sarcoma group of the French Federation of Cancer Centers (FNCLCC). Clinicopathologic factors were collected retrospectively and entered into a cooperative database. Tissue slides of all cases were jointly reviewed microscopically by the pathology subcommittee. Surgical treatment was performed on all but 6 (3%) patients. One hundred ninety-five patients (90%) were free of gross disease, with complete local control at the end of the initial treatment. The adjuvant treatment was radiotherapy in 78 patients (36%), chemotherapy in 19 patients (9%), and both in 61 patients (28%)., Results: The median follow-up was 3.5 years (range, 45 days to 12 years). Five-year actuarial rates of disease specific (DSS), metastasis free (MFS), and local recurrence free (LRFS) survival were 70%, 63.3%, and 62.7%, respectively. Multivariate analyses showed that the adverse prognostic factors independently associated with decreased disease specific survival were UICC/AJC Stage III + IVA (P < 0.00001; relative risk [RR], 3.27; 95% confidence interval [CI], 1.6-6.58), residual macroscopic disease following primary local therapy (P = 0.00024; RR, 3.99, CI, 2.04-7.82), deep tumor location (P = 0.0045; RR, 3.37; CI, 1.21-9.38), non-myxoid histology (P = 0.0056; RR, 9.28; CI, 1.03-83.41), and age older than 50 years (P = 0.037; RR, 2.19; CI, 1.04-4.61). Two factors were significantly related to MFS in the patients with the poorest prognosis: histopathologic Grade 3 (P < 0.0001, RR, 3.46; CI, 2.02-5.91) and tumor size greater than 8 cm in largest dimension (P = 0.0012; RR, 2.78; CI, 1.36-3.66). With regard to LRFS, patients who did not undergo radiotherapy had reduced local control (P = 0.0043; RR, 2.36; CI, 1.46-3.83)., Conclusions: Resection of all macroscopic disease was independently associated with improved disease specific survival and adjuvant radiotherapy significantly decreased the local relapse risk. Histopathologic grade was the most important prognostic factor for DSS and MFS.

Background: The major factor influencing the prognosis of cutaneous malignant melanoma (MMs) is the maximum thickness of the tumor as measured by Breslow's method. However, it has been reported that thin melanomas, which should have an excellent prognosis, may have the potential to metastasize, some with an unusually rapid course., Objective: Our purpose was to examine prognostic indicators in relation to unusually rapid aggressive behavior in patients with thin MMs (<0.76mm)., Methods: We describe nine cases of thin MM (<.76mm) that exhibited a recurrence or metastasis during a follow-up period ranging from 3 to 10 years, among computerized records of 1118 MMs treated in a multicenter epidemiologic study. The data obtained from these nine cases were compared with nonrecurring thin MM (149 cases) of the same cohort., Results: The particular aggressiveness of these thin melanomas was reflected by the short disease-free interval (3 years or less) in all ine patients. The recurring thin MM more frequently involved head and neck sites, occurred in male patients, and showed Clark's level III and IV., Conclusion: Our review suggests that the head and neck area is particularly involved by unusually rapidly recurring thin MM. Possible explanations are the specific problems of surgical management and the greater sun exposure of this location.

These recommendations regard the immunohistochemical evaluation of estrogen and progesterone receptors in paraffin sections of breast cancers. All the components of the procedure are dealt with: fixation, antigen retrieval, antibodies, controls, analysis and interpretation of immunostaining, report and quality assurance parameters. The purpose of these guidelines is to serve as a basis for standardization of techniques and results and to improve quality control.

Soft tissue tumors are a challenging group of tumors that presents wide morphologic variety. For pathologists, the degree of cellular differentiation, the cellular and nuclear polymorphism and the mitotic rate are major criteria for diagnosis. In image analysis, the architectural organization of such tumors shows local variations that can be understood as texture variations. This study introduced a method of measuring the architectural organization of soft tissue tumors from texture analysis of tissue sections at low magnification. We studied 40 cases of soft tissue tumors classified by pathologists into three groups according to their histologic patterns. Twelve texture parameters were calculated on subimages of 128 x 128 pixels. Our results show that tissue architecture evaluated by texture analysis provides good discrimination of myxoid, spindle cell and round cell tumors.

Conventional histologic grading of cystosarcoma phyllodes of the breast has not been entirely successful in the prognosis of recurrence or metastasis. Our study first developed a tumor grade classification based on computerized texture features and then compared the classification to conventional grading of these tumors. Evaluation of the tissue architecture of histologic sections was obtained by measuring nine texture features on an image analysis system. Forty cases of cystosarcoma phyllodes were studied. Each parameter was calculated on subimages of 128 x 128 pixels. This size resulted from a preliminary study that confirmed that the difference between texture primitives depends on the area of subimages. We also compared our series to a panel of 20 extramammary sarcomas. The results show that tissue architecture evaluated by texture analysis allows good discrimination between benign, borderline and malignant cystosarcoma phyllodes. Furthermore, extramammary sarcomas and malignant cystosarcoma phyllodes were discriminated well in most cases.

The use of prognostic factors to help select breast cancer patients for adjuvant therapy is of considerable concern to the oncology community. This need for selection of prognostically less favorable cases is stimulating investigators to identify new and more powerful prognostic factors. Unfortunately however, this identification process is becoming more confusing because of a lack of guidelines for investigators to use to study new factors and for reviewers and readers to use to evaluate papers on this topic. In this paper, we will describe across our experience the main problems encountered in the study of biological prognostic studies. Considering evaluation criteria to be developed in the future, it appears that only multicentric and multidisciplinary structures are able to define decisional trees based on technically and clinically validated parameters in particular patients subgroups. Such a structure exists at the european level ("Receptor Study Group" of the EORTC) and a similar structure has now been created in France to answer these questions.

In breast pathology, immunohistochemistry (IHC) allows the resolution of differential diagnostic problems regarding a primary tumor. With a basic antibody panel, it allows precise identification of undifferentiated, morphologically similar or unusual tumors. In case of doubt on invasiveness, IHC reveals the epithelial basement membrane and myoepithelial cells. A specific marker of breast tissue does not exist at the present time, but IHC guides the physician in the direction of breast in case of unknown secondary tumor or to confirm the primary breast site or to indicate the breast as primary site in case of two morphologically similar tumors. For the prognosis, IHC improves the detection of occult metastases (serous fluids, node, bone marrow, etc.). During the last few years, its indications have increased considerably with the possibility of performing, with paraffin slides, the detection of estrogen and progesterone receptors, growth factors and their receptors, oncoproteins, cell proliferation-related proteins, etc. The effects on the prognosis and chemotherapy sensitivity evaluation are obvious. But the pathologists must be very demanding because the clinical use of these new data by the physicians will be possible only after an excellent methodological and clinical validation in relation to the classical prognostic factors.

Expression of pS2 was studied by immunocytochemistry in normal breast tissue (n = 20), benign tumours (n = 9) and 145 breast cancers representative of the different histological types. pS2 immunostaining was scored as negative (D1 = 0-5% stained cells), positive (D2 = 5-75% stained cells) or highly positive (D3 > 75% stained cells). pS2 protein was evident in all normal breast samples examined. Six of nine benign lesions showed pS2 staining. In both cases, immunostaining was weaker than in breast cancers. Of breast cancers, 77/145 (53.1%) were pS2 positive, including 33.1% with intense staining. The presence of pS2 was not correlated with the age of patients, the size of the primary tumour, or lymph node status, but was correlated with histological grading and nuclear grading. pS2 expression was also correlated with menopausal status and oestrogen receptor status (59% of receptor-positive tumours were pS2 positive), but not to progesterone receptor status. pS2 expression in breast carcinomas is not a characteristic of specific histological types. Although this protein is predominantly expressed in oestrogen receptor-positive and differentiated tumours, it shows oestrogen-independent expression in about 30% of cases.