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BACKGROUND: Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date. PATIENTS AND METHODS: In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions). RESULTS: Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1. CONCLUSIONS: Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB , Medicina Genômica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Conventional chondrosarcoma is the second most common primary malignant bone tumor and usually occurs at older adult ages. It is rare in childhood and adolescence. CASE HISTORY: This case report presents the treatment course of a 13-year-old boy with a symptomatic chondrogenic tumor of the right distal femur. Histopathologically, an epiphyseal intermediate-grade chondrosarcoma (G2) was diagnosed. DISCUSSION: Based on the following case, potential radiological and histopathological differential diagnoses, such as chondroblastoma or chondroblastic osteosarcoma, are discussed against the background of current standards in orthopedic oncology.
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Neoplasias Ósseas , Condroblastoma , Condrossarcoma , Osteossarcoma , Adolescente , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Condroblastoma/diagnóstico por imagem , Condroblastoma/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/cirurgia , Epífises , Humanos , Masculino , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/cirurgiaRESUMO
Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.
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Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias de Células Epitelioides Perivasculares/terapia , HumanosRESUMO
Round-cell sarcomas represent highly malignant tumors that occur predominantly in children, adolescents, and young adults. Round-cell sarcomas are caused by recurrent translocations that involve certain transcription factors. Ewing's sarcoma, Ewing-like sarcomas (e.g. CIC-DUX positive or BCOR positive sarcomas), desmoplastic small round-cell tumors (DSRCTs), and alveolar rhabdomyosarcomas (ARMs) are typical examples of this particular group of sarcomas. These entities differ in their tumor genetics, which is correlated with immunohistochemical expression profiles and with clinical phenotypes. Classification should be based on molecular findings. Immunohistochemistry may serve as a surrogate marker.
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Sarcoma de Ewing , Sarcoma de Células Pequenas , Adolescente , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , Sarcoma de Ewing/patologia , Sarcoma de Células Pequenas/patologia , Adulto JovemRESUMO
Epithelioid soft tissue tumors consist exclusively of epithelioid tumor cells. Biphasic tumors are composed of both a spindle-cell and an epithelioid component. The rare mixed tumors of soft tissue show a broader variety of cellular and stromal differentiation but also include at least one, possibly several, epithelioid portions.The close morphological similarity of some of these entities with each other, as well as with the more frequent soft tissue metastases of carcinomas, carcinosarcomas, and melanomas, to malignant mesothelioma and certain lymphomas, can often make the correct diagnosis extremely difficult. Recent advances in the detection of certain molecular alterations (mostly chromosomal translocations) have contributed to changes in tumor classification but also to improved pathological diagnostics (e.g. through the development of potent diagnostic antibodies) and biological understanding.The present overview should help the pathologist in the diagnosis of these rare tumors through the classical approach of morphological pattern recognition. The most important entities are discussed and illustrated in more detail, with the incorporation of the latest immunohistochemical and molecular aspects and the differential diagnosis of similar tumors.
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Mesotelioma , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Mesotelioma/diagnóstico , Mesotelioma/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologiaRESUMO
Diagnostics and treatment of mesenchymal tumors (i.e. soft tissue sarcomas, gastrointestinal stromal tumors, and bone sarcomas) have changed dramatically in the past few years. Molecular and immunohistochemical biomarkers contribute significantly to improved diagnostics. They also play an increasing role in terms of clinical treatment decisions.Grading and tumor type-specific outcome data provide the basis for adjuvant chemotherapy of localized sarcomas. Recurrent gene fusions become more important as predictive biomarkers for targeted therapies in the context of systemic treatments. Immuno-oncology-based approaches are currently being studied in clinical trials, and the first responses of selected patients have been demonstrated. However, the role of predictive biomarkers in this field, such as PD-L1, still needs to be elucidated. Comprehensive genetic analyses of metastatic sarcomas will continue to identify additional therapeutic targets and the corresponding biomarkers.
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Neoplasias Ósseas , Tumores do Estroma Gastrointestinal , Sarcoma , Neoplasias de Tecidos Moles , Biomarcadores Tumorais , Neoplasias Ósseas/terapia , Quimioterapia Adjuvante , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Humanos , Sarcoma/diagnóstico , Neoplasias de Tecidos Moles/terapiaRESUMO
Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal neoplasms with features of both melanotic and smooth muscle differentiation. PEComa morphology is highly variable and encompasses epithelioid to spindle cells often with clear cytoplasm and prominent nucleoli. Molecularly, most PEComas are defined by a loss of function of the TSC1/TSC2 complex. Additionally, a distinct small subset of PEComas harboring rearrangements of the TFE3 (Xp11) gene locus has been identified. By presenting a series of three case reports with distinct features, we demonstrate diagnostic pitfalls as well as the importance of molecular work-up of PEComas because of important therapeutic consequences.
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Neoplasias de Células Epitelioides Perivasculares , Biomarcadores Tumorais , Humanos , Neoplasias de Células Epitelioides Perivasculares/diagnósticoRESUMO
Immuno-oncology related treatments have become standard of care for many tumor entities. Numerous additional indications are currently under investigation in ongoing clinical trials. Predictive biomarkers include microsatellite instability as well as tumor mutational burden. However, PD-L1 testing by immunohistochemistry (IHC) is already widely established as a biomarker in clinical routine for certain treatment decisions in non-small cell lung cancer, head and neck cancer and in urothelial carcinomas. More applications of that kind are expected to follow. Moreover, PD-L1 testing can provide clinicians with valuable information even if the test is not mandatory (i.â¯e., complementary diagnostics). PD-L1 staining requires a highly specific staining over a broad dynamic range. Sensitive and specific primary antibodies and suitable staining protocols are prerequisite. Selection of appropriate patients' materials, validation and contiguous quality assurance need to meet the highest standards. There are different scoring algorithms for PD-L1 stainings which are specific to tumor entities and certain clinical decisions. The tumor proportion score (TPS) is a PD-L1 measurement which is applied, for example, to lung cancer, head and neck cancer and melanomas. Within this approach, only membranous staining of tumor cells is regarded as a significant staining. In contrast, the combined positivity score (CPS) and inflammatory cell (IC) scoring include or are restricted to PD-L1 expression in certain inflammatory cells, respectively. CPS and IC scoring are standard measurements of PD-L1 in urothelial carcinoma.
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Antígeno B7-H1/análise , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Humanos , Imuno-Histoquímica , Neoplasias PulmonaresRESUMO
BACKGROUND: Fibroblast growth factor receptor (FGFR) signalling plays an important role in embryogenesis as well as in tumorigenesis. In current studies FGFR has proved to be a potential molecular target in a variety of solid tumours. In colorectal cancer (CRC) data on FGFR alterations is very sparse. However, there is a huge need for targeted therapies in this tumour entity with an incidence of 140,000 individuals (USA 2018) and a 5-year relative survival rate of only 14% in metastatic disease. OBJECTIVES: This article shall provide an overview of the FGFRs and the most frequent FGF ligand alterations in primary and metastatic CRC. RESULTS: In primary tumours and metastases various FGFR and FGF alterations can be observed. Primary tumours as well as metastases show FGFR alterations at the genomic (by fluorescence in situ hybridization) as well as on the ribonucleic acid (RNA) expression level (by RNA in situ hybridization). In both cohorts FGFR3 overexpression is the most frequent alteration and is associated with an unfavourable prognosis in metastases. CONCLUSIONS: FGFR3 overexpression defines a subgroup of metastatic colorectal cancers with an unfavourable prognosis. Since FGFR3 alterations can present a potential therapeutic target, patients with FGFR3 overexpression should be included into clinical studies with FGFR inhibitors.
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Neoplasias Colorretais , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias Colorretais/metabolismo , Humanos , Hibridização in Situ Fluorescente , Transdução de SinaisRESUMO
Primary sarcomas and sarcoma metastases are a rarity in the spleen. We report on the case of a 69-year-old male patient presenting with unclear abdominal symptoms and computed tomography (CT) revealed a tumor mass in the spleen. Histologically the tumor mass predominantly showed features of a spindle cell sarcoma with lymphoid infiltrates. The expression and amplification of MDM2 could be demonstrated by means of immunohistochemistry and fluorescence in situ hybridization (FISH). Furthermore, staging examinations did not reveal indications of any other primary tumors. These preliminary findings were suggestive of a dedifferentiated liposarcoma; however, in the further diagnostic work-up the tumor showed strong expression of CD21 and CD23 and was ultimately diagnosed as a follicular dendritic cell sarcoma (FDCS). The case emphasizes that MDM2 expression represents a possible pitfall in the diagnosis of spindle cell tumors. The differential diagnostic distinction between FDCS and a dedifferentiated liposarcoma is discussed.
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Lipossarcoma/genética , Lipossarcoma/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Sarcoma/genética , Sarcoma/patologia , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/patologia , Idoso , Diagnóstico Diferencial , Humanos , Lipossarcoma/cirurgia , Masculino , Sarcoma/cirurgia , Baço/patologia , Esplenectomia , Neoplasias Esplênicas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Antibodies against PD-1 and PD-L1 can cause strong and durable anti-tumor immune responses in non-small cell lung cancer (NSCLC). Immunohistochemistry for PD-L1 (PD-L1 IHC) was tested as a predictive biomarker. Several IHC assays and interpretation criteria were developed in parallel. AIM: The clinical significance of PD-L1 IHC in NSCLC and the optimum method for staining and interpretation of the results are the subject of ongoing studies. The diagnostic application of immunotherapy in NSCLC necessitates harmonization of PD-L1 IHC to obtain evidence for guidelines; therefore, a consensus opinion on a well-founded diagnostic mode of testing should be defined based on published studies and the results of the first German PD-L1 IHC harmonization study. METHODS: 1. Summary of the current data situation. 2. Evaluation of the first German PD-L1 IHC harmonization study (centralized, staining with PD-L1 IHC analogous to studies, 15 cases of NSCLC, 4 IHC study assays [288, 22C3, SP142 and SP263] and scoring by 9 pathologists). RESULTS: The use of PD-L1 IHC in NSCLC is suitable for identification of patients with an increased probability of a clinical benefit from immunotherapy. The various proportional cut-offs used to interpret the staining results can be summarized in a total score, which can be reproducibly assessed. The staining patterns of the four assays investigated were, however, not congruent in all situations. DISCUSSION: In principle, the use of PD-L1 IHC for assessment of the expression in tumor cells is a reliably determinable biomarker. Evaluation algorithms should be based on published clinical trials. For NSCLC approvals with obligatory PD-L1 IHC are to be expected but it remains to be seen to what extent PD-L1 IHC will be implemented in the clinical routine.
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Antígeno B7-H1/análise , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Algoritmos , Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imuno-Histoquímica , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Valor Preditivo dos Testes , PrognósticoRESUMO
BACKGROUND: The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by (68)Ga-PSMA PET/CT. METHODS: Retrospective analysis of 35 PCa patients underwent (68)Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n = 23) or before primary therapy of high-risk PCa (n = 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS: Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18-30) and 19.5 ng/ml (range 6-90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4-17) and 12 (range 8-29) per patient and the median number of positive lymph nodes was 1 (range 1-2) and 3 (2-3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS: This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by (68)Ga-PSMA PET/CT. The use of (68)Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies.
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Excisão de Linfonodo , Metástase Linfática/patologia , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Terapia de Alvo Molecular/métodos , Alemanha , Humanos , Sociedades MédicasRESUMO
Soft tissue tumors are often challenging for pathologists on the basis of morphology alone; therefore, tumor-specific chromosomal aberrations, such as translocations and fusions, amplifications or deletions can be diagnostically useful. Fluorescence in situ hybridization is widely used for the detection of most aberrations in routine diagnostics. Furthermore, reverse transcriptase PCR, sequencing and specific immunohistochemical assays are also applied. Next generation sequencing has already contributed to the identification of hitherto unknown aberrations. Molecular pathology is mainly used in sarcomas to discriminate between different tumor entities. In terms of personalized therapy and targeted treatment, molecular pathology can be utilized to detect predictive markers.
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Técnicas de Diagnóstico Molecular , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Aberrações Cromossômicas , Análise Citogenética , Análise Mutacional de DNA , Marcadores Genéticos/genética , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Medicina de Precisão , Prognóstico , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/terapiaRESUMO
BACKGROUND: Biliary tract cancers (BTCs) exhibit high mortality rates and significant heterogeneity in both clinical and molecular characteristics. This study aims to molecularly characterize a cohort of patients with BTC, with a specific focus on genomic alterations within homologous recombination repair (HRR) genes in a real-world setting. PATIENTS AND METHODS: We carried out a retrospective analysis on 256 patients with BTC treated at five Austrian centers and one German comprehensive cancer center between 2016 and 2023 utilizing comprehensive genomic profiling platforms to assess HRR status and its correlation with clinical outcomes after platinum-based chemotherapy. RESULTS: A total of 67 patients (27.5%) exhibited HRR gene mutations (HRRm), with the most common pathogenic alterations in BAP1 (9%), ARID1A (7.8%), and ATM (6.1%). Time to failure of the first-line strategy (TFS) between patients with HRRm and non-HRRm treated with platinum agents was 7.9 and 6.7 months, respectively [hazard ratio (HR) 0.89; P = 0.49]. The overall survival (OS) estimates at 6, 18, and 24 months were 82%, 45%, and 39% in the HRRm group (median 16.01 months) and 81%, 42%, and 22% in the HRR group (median 15.68 months), respectively (Fleming-Harrington test P = 0.0004; log-rank P = 0.022). Significance did not persist in the multivariate analysis (HR 0.72; 95% confidence interval 0.489-1.059; P = 0.095). An interaction between HRRm status and molecular-informed therapeutic strategies in later lines was noted. In the second-line treatment, OS following an irinotecan-based regimen was comparable to re-exposure to platinum-based agents (12.36 versus 10.13 months; HR 0.92; P = 0.85). No better outcome was noted for patients with HRRm versus patients with non-HRRm with second-line platinum agents (HR 1.45; P = 0.35). CONCLUSIONS: Patients with HRRm with BTC showed a potential advantage in OS following platinum-based first-line chemotherapy, presumably attributed to enhanced opportunities for targetable coalterations. Further investigation is needed to outline HRR within the scope of BTCs and detail a clinically meaningful sensitivity to platinum agents or targeted approaches with poly (ADP-ribose) polymerase (PARP) inhibitors.
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PURPOSE: Systemic-inflammatory response parameters (SIR) are known prognostic markers in different tumour entities, but have not been evaluated in patients with iCCA treated with systemic chemotherapy. Therefore, we evaluated the impact of different SIR markers on the clinical course of patients with advanced iCCA treated at our center. METHODS: SIR markers were retrospectively evaluated in 219 patients with iCCA at the West-German-Cancer-Center Essen from 2014 to 2019. Markers included neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), CRP, and the modified Glasgow-Prognostic-Score (mGPS), which were correlated with clinico-pathological findings, response to chemotherapy (ORR), progression-free (PFS) and overall survival (OS) using Kaplan-Meier analyses, and Cox proportional models. RESULTS: Median overall survival (OS) of the entire cohort was 14.8 months (95% CI 11.2-24.4). Median disease-free survival (DFS) in 81 patients undergoing resection was 12.3 months (95% CI 9.7-23.1). The median OS from start of palliative CTX (OSpall) was 10.9 months (95% 9.4-14.6). A combined Systemic Inflammatory Score (SIS) comprising all evaluated SIR markers correlated significantly with ORR, PFS, and OSpall. Patients with a high SIS (≥ 2) vs. SIS 0 had a significantly inferior OSpall (HR 8.7 95% CI 3.71-20.38, p < 0.001). Multivariate analysis including known prognostic markers (ECOG, CA19-9, LDH, and N- and M-status) identified the SIS as an independent prognostic factor. CONCLUSIONS: Inflammatory markers associate with inferior survival outcomes in patients with iCCA. A simple SIS may guide treatment decisions in patients treated with systemic chemotherapy.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Estudos Retrospectivos , Inflamação/patologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Linfócitos/patologia , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologiaRESUMO
BACKGROUND: Pancreatic cancer has a dismal prognosis. One reason is resistance to cytotoxic drugs. Molecularly matched therapies might overcome this resistance but the best approach to identify those patients who may benefit is unknown. Therefore, we sought to evaluate a molecularly guided treatment approach. MATERIALS AND METHODS: We retrospectively analyzed the clinical outcome and mutational status of patients with pancreatic cancer who received molecular profiling at the West German Cancer Center Essen from 2016 to 2021. We carried out a 47-gene DNA next-generation sequencing (NGS) panel. Furthermore, we assessed microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status and, sequentially and only in case of KRAS wild-type, gene fusions via RNA-based NGS. Patient data and treatment were retrieved from the electronic medical records. RESULTS: Of 190 included patients, 171 had pancreatic ductal adenocarcinoma (90%). One hundred and three patients had stage IV pancreatic cancer at diagnosis (54%). MMR analysis in 94 patients (94/190, 49.5%) identified 3 patients with dMMR (3/94, 3.2%). Notably, we identified 32 patients with KRAS wild-type status (16.8%). To identify driver alterations in these patients, we conducted an RNA-based fusion assay on 13 assessable samples and identified 5 potentially actionable fusions (5/13, 38.5%). Overall, we identified 34 patients with potentially actionable alterations (34/190, 17.9%). Of these 34 patients, 10 patients (10/34, 29.4%) finally received at least one molecularly targeted treatment and 4 patients had an exceptional response (>9 months on treatment). CONCLUSIONS: Here, we show that a small-sized gene panel can suffice to identify relevant therapeutic options for pancreatic cancer patients. Informally comparing with previous large-scale studies, this approach yields a similar detection rate of actionable targets. We propose molecular sequencing of pancreatic cancer as standard of care to identify KRAS wild-type and rare molecular subsets for targeted treatment strategies.
Assuntos
Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Genômica , Neoplasias PancreáticasRESUMO
Postradiation cutaneous vascular lesions after treatment of breast carcinoma comprise a heterogeneous group of benign, atypical, and malignant lesions and are best regarded as points along a morphological spectrum. We analyzed a series of cutaneous angiosarcomas after treatment of breast cancer in comparison with control cases and cases of atypical vascular lesions with special emphasis on the expression and amplification of MYC. The 66 cases were divided into control cases (5), cases in which a slight vascular proliferation was seen after radiotherapy of breast cancer (12), cases of atypical vascular lesions after radiotherapy (16), cases of postradiation cutaneous angiosarcomas (25), and cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (8). None of the control cases (2 M, 3 F, 20-76 years), of cases showing slight vascular proliferation, dermal fibrosis and inflammation after radiotherapy of breast cancer (12 F, 48-79 years), of cases of atypical vascular lesions after radiotherapy (16 F, 29-81 years), and of cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (3 M, 5 F, 25-92 years) showed an amplification of MYC by FISH analysis. In striking contrast, in all cases of postradiation cutaneous angiosarcomas (25 F, 46-95 years), MYC amplification was found by FISH analysis in a variable number of counted nuclei. Immunohistochemically, strong positive nuclear staining for MYC and prox-1 was seen in cases of postradiation cutaneous angiosarcoma, whereas control cases and cases of atypical vascular proliferation after radiotherapy were negative for MYC, and stained only focally positive for prox-1 in a number of cases. In conclusion, the presence of MYC amplification represents an important additional diagnostic tool in the distinction of postradiation cutaneous angiosarcomas from atypical vascular lesions after radiotherapy. Immunohistochemical stainings for MYC are useful for mapping of these lesions and for careful tumor margin control.