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1.
Ann Pathol ; 41(6): 507-520, 2021 Nov.
Article in French | MEDLINE | ID: mdl-34393014

ABSTRACT

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology.


Subject(s)
Breast Neoplasms , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Receptor, ErbB-2/genetics
2.
NPJ Breast Cancer ; 7(1): 41, 2021 Apr 16.
Article in English | MEDLINE | ID: mdl-33863896

ABSTRACT

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

3.
PLoS One ; 16(2): e0246958, 2021.
Article in English | MEDLINE | ID: mdl-33630918

ABSTRACT

BACKGROUND: Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France. METHODS: The nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed. RESULTS: Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10-6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per. CONCLUSIONS: This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials.


Subject(s)
Sarcoma/epidemiology , Sarcoma/pathology , Adolescent , Adult , Aged , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Neoplasm Grading , Prospective Studies , Sarcoma/classification , Sarcoma/diagnosis , World Health Organization , Young Adult
4.
Mod Pathol ; 34(1): 116-130, 2021 01.
Article in English | MEDLINE | ID: mdl-32728225

ABSTRACT

Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.


Subject(s)
Algorithms , Anus Neoplasms/pathology , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Adult , Aged , Anus Neoplasms/epidemiology , Carcinoma, Squamous Cell/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Progression-Free Survival , Treatment Outcome
6.
Ann Pathol ; 39(6): 383-398, 2019 Dec.
Article in French | MEDLINE | ID: mdl-31257035

ABSTRACT

Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).


Subject(s)
Breast Neoplasms/pathology , Breast/pathology , Lymph Nodes/pathology , Neoadjuvant Therapy , Specimen Handling/standards , Biomarkers, Tumor , Biopsy/methods , Biopsy/standards , Breast Neoplasms/chemistry , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Chemotherapy, Adjuvant/standards , Drug Screening Assays, Antitumor , Female , France , Humans , Lymph Nodes/drug effects , Lymph Nodes/surgery , Medical Records/standards , Microscopy , Neoplasm, Residual/pathology , Prognosis , Sentinel Lymph Node Biopsy/methods , Specimen Handling/methods , Treatment Outcome , Tumor Burden/drug effects
7.
Oncologist ; 24(8): e775-e783, 2019 08.
Article in English | MEDLINE | ID: mdl-31073021

ABSTRACT

BACKGROUND: Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management. MATERIALS AND METHODS: Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed. RESULTS: A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center. CONCLUSION: Initial diagnostic management requires improvement, especially outside of specialized centers. IMPLICATIONS FOR PRACTICE: This article supports the essential need to refer patients with soft tissue tumors to specialized centers to improve the management of sarcomas beginning at the diagnostic phase. Indeed, the reported data were very similar to those already described at the national level of the NetSarc network and indicate the necessity to keep raising awareness about this simple issue: early referral to reference centers will save lives.


Subject(s)
Guideline Adherence/standards , Sarcoma/surgery , Soft Tissue Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Cancer Care Facilities/standards , Disease Management , Female , France , Humans , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Sarcoma/diagnosis , Soft Tissue Neoplasms/diagnosis , Young Adult
8.
Br J Cancer ; 120(9): 913-921, 2019 04.
Article in English | MEDLINE | ID: mdl-30899086

ABSTRACT

BACKGROUND: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of MA cancers. METHODS: Centrally assessed biopsies for AR, ER, PR, HER2 and Ki67 by IHC were classified into six subtypes: MA, triple-negative (TN) basal-like, luminal A, luminal B HER2 negative, luminal B HER2 positive and "other". The two main objectives were the pCR rates and survival outcomes in the overall MA subtype (and further divided by HER2 status) and the remaining five subtypes. RESULTS: IHC subtyping was obtained in 846 eligible patients. Ninety-three (11%) tumours were classified as the MA subtype. Both IHC and GEA data were available for 64 patients. In this subset, IHC concordance was 88.3% in identifying MA tumours compared with GEA. Within the MA subtype, pCR was observed in 33.3% of the patients (95% CI: 29.4-43.9) and the 5-year recurrence-free interval was 59.2% (95% CI: 48.2-68.6). Patients with MA and TN basal-like tumours have lower survival outcomes. CONCLUSIONS: Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , ErbB Receptors/metabolism , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Receptor, ErbB-2/metabolism , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Survival Rate , Treatment Outcome
9.
Surg Innov ; 25(4): 313-322, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29732957

ABSTRACT

BACKGROUND: Intraoperative decision of the level of distal resection in rectal cancer is often imprecise, based exclusively on digital examination and pretherapeutic imaging. DESIGN: Prospective, single institution, nonrandomized trial ( ClinicalTrial.gov identification no. NCT01887509) to evaluate the contribution of probe-based confocal laser endomicroscopy (pCLE) to establish the optimal resection margin of rectal adenocarcinoma. The primary outcome was the concordance in the identification of lower tumor margins between pCLE and histopathology. For each patient, pCLE examination was performed on nonneoplastic and neoplastic aspects of the distal tumor margin, before and after neoadjuvant chemoradiation, or preceding surgery, if chemoradiation was not required. Biopsies were taken at the same locations. The intraclass correlation coefficient was determined. RESULTS: Twenty-one patients were enrolled. Thirteen patients completed the full study. Six patients completed imaging only before chemoradiation. Two patients retracted their consent after inclusion. A total of 134 videos and corresponding histopathology samplings were analyzed. The sensitivity and specificity of in vivo pCLE interpretation were 0.915 (95% confidence interval [CI] = 0.840-0.970) and 0.736 (95% CI = 0.657-0.821), respectively. The sensitivity and specificity of the blinded pCLE reinterpretation were 0.930 (95% CI = 0.858-0.980) and 0.688 (95% CI = 0.600-0.770), respectively. No deep layer tumor infiltration was encountered in the samplings with superficial healthy layers. The intraclass correlation coefficient for in vivo pCLE interpretation and blinded pCLE reinterpretation were 0.747 (95% CI = 0.257-0.993) and 0.766 (95% CI = 0.280-0.995), respectively. CONCLUSIONS: This supports the concordance between pCLE and histopathology in identifying the "tumor-free" limit of a rectal tumor preceding resection.


Subject(s)
Adenocarcinoma/diagnostic imaging , Colonoscopy/methods , Microscopy, Confocal/methods , Rectal Neoplasms/diagnostic imaging , Aged , Colonoscopy/instrumentation , Female , Humans , Male , Microscopy, Confocal/instrumentation , Middle Aged , Prospective Studies
10.
Head Neck ; 39(1): 32-36, 2017 01.
Article in English | MEDLINE | ID: mdl-27299703

ABSTRACT

BACKGROUND: The American Thyroid Association (ATA) recommends using ultrasound-guided fine-needle aspiration (FNA) in order to evaluate supracentimetric and suspect thyroid nodules. The purpose of this study was to evaluate the effective use of FNA before surgery for nodules over 3 cm in diameter. METHODS: In this retrospective study, we analyzed the results of ultrasound-guided FNA and postoperative histological analysis in 843 nodules >3 cm. RESULTS: The FNA was informative in 42.6%. The correlation with the final histological analysis was 94.8% for benign nodules and 71.0% for malignant nodules. The FNA had a positive predictive value of 71%, a specificity of 97%, a sensitivity of 56%, and a 4.7% rate of false-negative results. CONCLUSION: Because there is a nonnegligible FNA risk of error, notably allowing the evolution of a cancer in 1 of 20 cases, the FNA data should not delay surgical intervention for potentially suspect nodules >3 cm in diameter. © 2016 Wiley Periodicals, Inc. Head Neck 39: 32-36, 2017.


Subject(s)
Biopsy, Fine-Needle , Thyroid Nodule/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Thyroid Nodule/surgery , Thyroidectomy , Young Adult
11.
Lancet Oncol ; 17(4): 532-538, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26970672

ABSTRACT

BACKGROUND: Advances in molecular genetics of sarcoma have enabled the identification of type-specific aberrations. We aimed to assess the clinical effect of systematic implementation of molecular assays to improve sarcoma misdiagnosis. METHODS: In this multicentre, observational study, we recruited patients from 32 centres of the French Sarcoma Group/Reference Network in Pathology of Sarcomas. Eligibility criteria included: biopsy or surgical resection; suspicion of: dermatofibrosarcoma protuberans (cohort 1), dedifferentiated liposarcoma (cohort 2), Ewing's sarcoma family of tumours (cohort 3), synovial sarcoma (cohort 4), alveolar rhabdomyosarcoma (cohort 5), and myxoid or round cell liposarcoma (cohort 6); review by one sarcoma-expert pathologist; availability of frozen material (except for cohort 1 of patients with dermatofibrosarcoma protuberans because anti-CD34 immunohistochemistry is performed on paraffin-embedded tissue); and patient information. For each case, the pathologist made one primary diagnosis followed by up to two differential diagnoses, based on histological characteristics only. Each diagnosis was classified as certain, probable, or possible. For each case to determine the molecular classification, we did fluorescence in-situ hybridisation on paraffin-embedded samples. We also did comparative genomic hybridisation and quantitative PCR (cohort 2) or reverse transcriptase PCR (cohorts 3-6) on frozen and paraffin-embedded samples. We made a final diagnosis based on the molecular results. The clinical effect of diagnosis correction was assessed by a board of experts. FINDING: Between June 22, 2009, and Oct 30, 2012, 395 patients were enrolled in the study, of which 384 were eligible for inclusion. The diagnosis was eventually modified by molecular genetics for 53 patients: eight (16%) of 50 patients with dermatofibrosarcoma (cohort 1), seven (23%) of 30 patients with dedifferentiated liposarcoma (cohort 2), 13 (12%) of 112 with Ewing's sarcoma family of tumours (cohort 3), 16 (16%) of 97 patients with synovial sarcoma (cohort 4), seven (15%) of 46 patients with alveolar rhabdomyosarcoma (cohort 5), and two (4%) of 49 patients with myxoid or round cell liposarcoma (cohort 6), with an effect on primary management or prognosis assessment in 45 cases. INTERPRETATION: Molecular genetic testing should be mandatory for diagnostic accuracy of sarcoma and appropriate clinical management, even when histological diagnosis is made by pathologist experts in this field. FUNDING: French National Cancer Institute and Nice University Hospital.


Subject(s)
Dermatofibrosarcoma/diagnosis , Liposarcoma/diagnosis , Pathology, Molecular , Sarcoma/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Comparative Genomic Hybridization , Dermatofibrosarcoma/genetics , Dermatofibrosarcoma/pathology , Diagnosis, Differential , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Immunohistochemistry/methods , Liposarcoma/genetics , Liposarcoma/pathology , Male , Middle Aged , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Prognosis , Sarcoma/classification , Sarcoma/genetics , Sarcoma/pathology
12.
Pathology ; 47(4): 320-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25938344

ABSTRACT

MET pathway is a promising target in non-small cell lung cancers (NSCLC) requiring companion tests. The aim of this study was to compare MET expression/gene copy number in a Caucasian population of NSCLC patients.We analysed 201 NSCLC, with 141 adenocarcinomas classified according to 2011 IASLC recommendations, for MET expression by immunohistochemistry (IHC) and gene copy number (GCN) by silver in situ hybridisation (SISH) on tissue microarrays. Mutations in EGFR, KRAS, BRAF, HER2, PIK3CA genes and ALK rearrangements were determined.MET overexpression was observed in 44% and a high MET GCN (≥5 copies) in 14%. MET CGN was correlated with MET expression, regardless of IHC scores (p < 0.001) but only 31% of MET overexpressed cases were SISH positive. MET overexpression/GCN number was more frequent in ADC than the other types (p < 0.001), the highest in high grade (74%/34%) and sarcomatoid ADC (86%/43%). Mutations of current genes or ALK rearrangements were identified in overexpressed or amplified MET cases. MET overexpression was an independent prognostic factor for overall survival in non-smoker NSCLC in univariate (p = 0.01) and multivariate (p = 0.01) analyses.MET overexpression is more frequent than MET high GCN, particularly in high grade ADC, regardless of EGFR, KRAS, BRAF, HER2, PIK3CA and ALK status in NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Gene Dosage , Lung Neoplasms/genetics , Proto-Oncogene Proteins c-met/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/classification , Carcinoma, Non-Small-Cell Lung/metabolism , Cohort Studies , Female , Humans , Immunohistochemistry , In Situ Hybridization , Lung Neoplasms/classification , Lung Neoplasms/metabolism , Male , Middle Aged , Proto-Oncogene Proteins c-met/biosynthesis , Retrospective Studies , Tissue Array Analysis , White People
13.
Appl Immunohistochem Mol Morphol ; 23(3): 230-5, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25747531

ABSTRACT

Heterologous differentiation in myxoid liposarcoma is a rare phenomenon. Few cases have been reported thus far, often without molecular assays, and the concept of "dedifferentiated" myxoid liposarcoma remains controversial. We describe a primary myxoid liposarcoma with chondroid and osseous components affecting the right thigh of a 27-year-old woman. We wondered whether these areas represented dedifferentiated components or simply metaplasia, and performed fluorescent in situ hybridization and array comparative genomic hybridization assays in the myxoid liposarcoma component and chondroid component. Fluorescent in situ hybridization analysis demonstrated a DDIT3 gene rearrangement in both components; array comparative genomic hybridization analysis did not detect any gain or loss of DNA regions in both components. Our results, demonstrating that both components have the same molecular alterations, suggest that heterologous components seen in some myxoid liposarcomas reflect a metaplastic phenomenon and not a real dedifferentiation phenomenon, challenging the concept of "dedifferentiated" myxoid liposarcoma.


Subject(s)
Bone Neoplasms , Gene Rearrangement , Liposarcoma, Myxoid , Neoplasm Proteins , Transcription Factor CHOP , Adult , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Comparative Genomic Hybridization , Female , Humans , In Situ Hybridization, Fluorescence , Liposarcoma, Myxoid/genetics , Liposarcoma, Myxoid/metabolism , Liposarcoma, Myxoid/pathology , Metaplasia , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Thigh/pathology , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolism
14.
Ann Pathol ; 34(5): 366-72, 2014 Oct.
Article in French | MEDLINE | ID: mdl-25439989

ABSTRACT

Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS' update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Immunohistochemistry/methods , In Situ Hybridization/methods , Receptor, ErbB-2/analysis , Receptors, Steroid/analysis , Breast Neoplasms/pathology , Female , Fixatives , France , Histological Techniques , Humans , Prognosis , Quality Control , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Specimen Handling/methods
15.
Ann Pathol ; 34(5): 352-65, 2014 Oct.
Article in French | MEDLINE | ID: mdl-25439988

ABSTRACT

International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse. Pre-analytical issues and updated scoring criteria (especially for equivocal cases) are detailed, in order to decrease the occurrence of false negative cases. In the era of personalized medicine, pathologists are more than ever involved in the quality of oncotheranostic biomarker evaluation.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Receptor, ErbB-2/analysis , Breast Neoplasms/drug therapy , False Negative Reactions , Female , France , Humans , Immunohistochemistry/methods , In Situ Hybridization , In Situ Hybridization, Fluorescence , Neoplasm Metastasis/pathology , Neoplasm Recurrence, Local , Prognosis
16.
Bull Cancer ; 100(10): 963-71, 2013 Oct.
Article in French | MEDLINE | ID: mdl-24095719

ABSTRACT

Sarcomas represent a complex and heterogeneous group of rare malignant tumors and their correct diagnosis is often difficult. Recent molecular biological techniques have been of great diagnostic use and there is a need to assess the cost of these procedures in routine clinical practice. Using prospective and observational data from eight molecular biology laboratories in France, we used "microcosting" method to assess the cost of molecular biological techniques in the diagnosis of five types of sarcoma. The mean cost of fluorescence in situ hybridization (FISH) was 318 € (273-393) per sample; mean reverse transcription polymerase chain reaction (RT-PCR) cost ranged from 300 € (229-481) per formalin-fixed, paraffin-embedded specimen to 258 € (213-339) per frozen specimen; mean quantitative polymerase chain reaction (Q-PCR) cost was 184 € (112-229) and mean CGH-array cost was 332 € (329-335). The cost of these recently implemented techniques varied according to the type of sarcoma; the method of tissue collection and local organizational factors including the level of local expertise and investment. The cost of molecular diagnostic techniques needs to be balanced against their respective performance.


Subject(s)
Comparative Genomic Hybridization/economics , In Situ Hybridization, Fluorescence/economics , Paraffin Embedding/economics , Rare Diseases/diagnosis , Real-Time Polymerase Chain Reaction/economics , Reverse Transcriptase Polymerase Chain Reaction/economics , Sarcoma/diagnosis , Costs and Cost Analysis , Dermatofibrosarcoma/diagnosis , Dermatofibrosarcoma/genetics , France , Humans , Liposarcoma/diagnosis , Liposarcoma/genetics , Memory, Episodic , Rare Diseases/genetics , Rhabdomyosarcoma, Alveolar/diagnosis , Rhabdomyosarcoma, Alveolar/genetics , Sarcoma/genetics , Sarcoma, Ewing/diagnosis , Sarcoma, Ewing/genetics , Sarcoma, Synovial/diagnosis , Sarcoma, Synovial/genetics , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics
17.
Ann Pathol ; 30(5): 357-73, 2010 Oct.
Article in French | MEDLINE | ID: mdl-21055523

ABSTRACT

In Europe, patients who may benefit from an HER2 targeted drug are currently selected by immunohistochemistry (IHC). In situ hybridization (ISH) techniques should be used for complementary assessment of ambiguous 2+ IHC cases and for the calibration of the IHC technique. Eligibility to an HER2 target treatment is defined by an HER2 positive status being IHC test 3+ or 2+ amplified. Reliable detection of HER2 status is essential to the appropriate usage of HER2 targeted drugs because its specificity is limited to tumors overexpressing HER2. It is essential that the IHC evaluation of the HER2 status of a mammary carcinoma is optimized and reliable. This GEFPICS' guidelines look over the different steps of the IHC technique, the controls and, the rules for interpretation. Once acquired, this knowledge must be perpetuated by the observation of rules of good technical practice (internal and external controls, quality assurance programs).


Subject(s)
Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Receptor, ErbB-2/analysis , France , Humans , Immunohistochemistry/standards , In Situ Hybridization/standards , Quality Control , Records
18.
Breast Cancer Res Treat ; 124(2): 387-91, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20824324

ABSTRACT

Absence of hormonal receptors (HR) expression is a predictive factor of high pathologic complete response (pCR) rate after neo-adjuvant chemotherapy. However, HR-positive tumors are less chemosensitive. In the present study, we evaluated the predictive value of estrogen (ER) and progesterone (PgR) semi-quantitative expression in patients with HR-positive tumors treated uniformly with antracycline-based neoadjuvant chemotherapy without hormonal treatment. Value of HR expression as a predictive factor was then evaluated in a multivariate analysis with tumor grade, Ki67 index and HER2 expression. From January 2000 and December 2006, 177 patients with HR-positive breast ductal invasive carcinoma ≥2 cm in its largest diameter were treated with six cycles of an anthracycline-based neo-adjuvant chemotherapy. Tumor grade, ER, PgR, HER2 status and Ki67 index were determined on microbiopsy performed before chemotherapy. A semi-quantitative evaluation of ER and PgR expression by IHC was performed using the Barnes'score. pCR rate was significantly different (P < 0.001) according to the ER expression score. pCR rate was 28% for low score, 9% for medium score and 3% for high score. On the contrary, pCR rate was not significantly different (P = 0.49) according to the PgR expression score. In the multivariate analysis, ER expression score (P = 0.0002) and Ki67 index (P = 0.02) were the only predictive factors of response for HR-positive tumors. pCR after anthracycline-based chemotherapy is significantly correlated with the ER expression score.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/analysis , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Neoplasms, Hormone-Dependent/drug therapy , Receptors, Estrogen/analysis , Adult , Antibiotics, Antineoplastic/administration & dosage , Biopsy, Needle , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/chemistry , Carcinoma, Ductal, Breast/pathology , Chemotherapy, Adjuvant , Chi-Square Distribution , Cyclophosphamide/administration & dosage , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Logistic Models , Neoadjuvant Therapy , Neoplasm Staging , Neoplasms, Hormone-Dependent/chemistry , Neoplasms, Hormone-Dependent/pathology , Patient Selection , Predictive Value of Tests , Receptor, ErbB-2/analysis , Receptors, Progesterone/analysis , Retrospective Studies , Risk Assessment , Risk Factors , Treatment Outcome
19.
Eur J Cancer ; 42(17): 2946-53, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16989997

ABSTRACT

The accurate determination of HER-2 in invasive breast cancer has become a critical issue, particularly in the context of the results of recent trastuzumab (Herceptin((R))) adjuvant trials. This multicentre study evaluated inter-observer reproducibility in interpretation of HER-2 immunostains performed in different laboratories according to their in-house technique. A total of 74 HER-2 immunostains were evaluated by 16 pathologists and by a central review committee. As determined by central review, the HER-2 score was 0 in 33 cases (44%), 1+ in 10 cases (13%), 2+ in 9 cases (12%) and 3+ in 23 cases (31%). The overall kappa value was good (kappa=0.75). Agreement was excellent for the 0/1+ group (kappa=0.85) and for the 3+ group (kappa=0.82). As expected, the score 2+ group showed poor agreement (kappa=0.38). A quality assurance process showed that ring studies and adherence to national guidelines greatly improve inter-observer reproducibility.


Subject(s)
Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Female , Humans , Immunohistochemistry/standards , Middle Aged , Observer Variation
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