FILOMENA MARINO CARVALHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
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- Triple-negative breast cancer: from none to multiple therapeutic targets in two decades(2023) CARVALHO, Filomena MarinoTriple-negative breast cancers (TNBCs) are more likely to occur in younger patients and have a poor prognosis. They are highly heterogeneous tumors consisting of different molecular subtypes. The only common characteristic among them is the absence of targets for endocrine therapy and human epidermal growth factor receptor 2 (HER2) blockade. In the past two decades, there has been an increased understanding of these tumors from a molecular perspective, leading to their stratification according to new therapeutic strategies. TNBC has ushered breast carcinomas into the era of immunotherapy. The higher frequency of germline BRCA mutations in these tumors enables targeting this repair defect by drugs like PARP inhibitors, resulting in synthetic lethality in neoplastic cells. Additionally, we have the identification of new molecules to which this generation of smart drugs, such as antibody-drug conjugates (ADCs), are directed. In this review, we will discuss the trajectory of this knowledge in a systematic manner, presenting the molecular bases, therapeutic possibilities, and biomarkers.
conferenceObject Clinical, psychological, and molecular aspects of a large androgen insensitivity syndrome cohort(2023) BATISTA, Rafael Loch; INACIO, Marlene; AFONSO, Ane Caroline; CARVALHO, Filomena; RAMOS, Raquel; CRAVEIRO, Flora; DALLAGO, Renata; FERRARI, Maria Tereza; BATATINHA, Julio; NISHI, Miriam; DOMENICE, Sorahia; MENDONCA, Berenice Bilharinho- HER2 Testing in Breast Carcinoma Very Low Concordance Rate Between Reference and Local Laboratories in Brazil(2011) WLUDARSKI, Sheila Cristina Lordelo; LOPES, Lisandro Ferreira; SILVA, Tacio R. Berto e; CARVALHO, Filomena M.; WEISS, Lawrence M.; BACCHI, Carlos E.Breast cancer accounts for approximately one quarter of all cancers in females. HER2 gene amplification or HER2 protein overexpression, detected in about 20% of breast carcinomas, predicts a more aggressive clinical course and determines eligibility for targeted therapy with trastuzumab. HER2 testing has become an essential part of the clinical evaluation of all breast carcinoma patients, and accurate HER2 results are critical in identifying patients who may be benefited from targeted therapy. This study investigated the concordance in the results of HER2 immunohistochemistry assays performed in 500 invasive breast carcinomas between a reference laboratory and 149 local laboratories from all geographic regions of Brazil. Our results showed an overall poor concordance (171 of 500 cases, 34.2%) regarding HER2 results between local and reference laboratories, which may be related to the low-volume load of HER2 assays, inexperience with HER2 scoring system, and/or technical issues related to immunohistochemistry in local laboratories. Standardization of HER2 testing with rigorous quality control measures by local laboratories is highly recommended to avoid erroneous treatment of breast cancer patients.
- Successful Pre-Treatment Ovarian Fresh Tissue Transplantation in a Cervical Cancer Patient Undergoing Radiation Therapy: A Case Report(2023) BERTOLAZZI, Marilia A.; GENTA, Maria Luiza Nogueira Dias; CARVALHO, Filomena; BARACAT, Edmund C.; CARVALHO, Jesus PaulaCervical cancer is one of the most frequent gynecological malignancies in Brazil, and most of the patients require pelvic radiotherapy as part of oncological treatment.Pelvic radiotherapy induces ovarian premature insufficiency in pre-menopausal women. This condition impacts the life quality and increases the risk of osteoporosis, obesity, cardiovascular, and neurodegenerative diseases in the middle and long term.Most of these patients have no access to hormonal replacement therapy. Techniques such as ovarian transposition have questionable results when aiming to preserve ovarian function. In this context, a promising alternative is the implantation of fresh ovarian tissue, outside the radiotherapy field, in the abdominal cavity (orthotopic implantation) or in other sites such as the forearm, breast, or subcutaneous tissue (heterotopic implantation).Here we report a successful case of autologous implantation of fresh ovarian tissue in the inner thigh of a young patient with advanced cervical cancer, who was a candidate for concurrent chemoradiotherapy.
- Tumor-Infiltrating Lymphocytes and Tumor- Stroma Ratio on Early-Stage Cervix Carcinoma: Prognostic Value of Two Distinct Morphological Patterns of Microenvironment(2023) LARRE, Ailma; FERNANDES, Raquel C.; GERBASI, Giovana J.; CARVALHO, Filomena M.Background Tumor progression is influenced by the complex network of different cellular elements that make up its microenvironment. Tumor-infiltrating lymphocytes (TILs) and stroma characteristics reflect two faces of the intricate mechanisms involved in the tumor-host interaction and can be easily evaluated by routine histological examination. Their prognostic value could be demonstrated in different tumor tumor types, but they are poorly explored in cervical cancer. Methodology In this retrospective study, we analyzed the association of TILs, tumor-stroma ratio (TSR), and pattern of stromal fibroblasts with prognosis and classical clinicopathological variables. We studied 61 patients with early-stage cervical cancer. We reviewed histological type, tumor grade, Silva pattern of invasion for adenocarcinomas, tumor thickness, depth of stromal invasion, lymph vascular space invasion, and lymph node status. The median follow-up was 37.77 months (range 4.77 to 112.37 months). Results The TSR did not correlate with any clinicopathological features or disease-free and overall survival. On the other hand, the reactive pattern of stroma composed of larger fibroblasts and less collagenization was associated with the FIGO IB2 stage (p=0.04), larger tumor (p=0.03), and deeper infiltration (p=0.005). There were more recurrences in the group of reactive stroma (33.13% vs. 11.5%), although the difference did not reach statistical significance. Reactive stroma was associated with lower survival free of recurrence (p=0.05) and overall survival (p=0.009). High TILs were associated with squamous cell type (p=0.003), higher tumor grade (p=0.02), and more LVSI (p=0.02). Tumors with higher TILs presented higher free recurrence interval (p=0.06) and overall survival (p=0.03). No association was observed between stroma characteristics and TILs. Conclusions Our study suggested that although immune activation and stromal changes are important features of microenvironment remodeling during tumoral progression, they are independent, following distinct carcinogenetic pathways. Pathological assessment of stroma characteristics and TILs adds significant prognostic information and demonstrates how a simple routine laboratory assessment can generate a better understanding of biological phenomena.
- Immune checkpoint inhibitors: here to stay(2023) CARVALHO, Filomena Marino; DIZ, Maria Del Pilar Estevez; CARVALHO, Jesus Paula
- Mucinous Cystadenoma Arising in a Uterine Isthmocele: A Case Report(2023) CARVALHO, Jesus Paula; SILVA, Alexandre Silva e; KLEINE, Rodolpho Truffa; BERTOLAZZI, Marilia Albanezi; FERNANDES, Rodrigo Pinto; CARVALHO, Filomena MarinoIsthmocele is a discontinuation of the myometrium at the uterine scar site in a patient with a previous cesarian section (CS). The cause of isthmocele appears to be multifactorial. Poor surgical technique, low incision location, uterine retroflection, obesity, smoking, inadequate healing of scars, and maternal age are possible related factors. Most patients with this condition are asymptomatic. However, women can present with postmenstrual bleeding, pelvic pain, subfertility, dysmenorrhea, infertility, and scar abscess. Brazil has one of the world's highest cesarean section rates. One of the consequences of the rising rate of CS is the isthmocele, an emerging female health problem. Here we report a case of mucinous cystadenoma arising in a uterine isthmocele, a complication, as far as we could investigate, not yet described in the literature.
- Gemcitabine-Induced Radiation Recall Phenomenon in Cervical Cancer: A Case Report(2023) CARVALHO, Jesus Paula; FREITAS, Daniela; HANNA, Samir; VELHO, Isabela A.; CARVALHO, Filomena M.The radiation recall phenomenon is a rare, massive inflammatory reaction induced by some chemotherapeutic agents in previously irradiated areas. When it occurs in the pelvis it looks like a recurrence. Recognizing this phenomenon is paramount to avoiding unnecessary surgical intervention and complications. Symptoms manifest as dermatitis, mucositis, myositis, esophagitis, colitis, proctitis, and pneumonitis in areas within the irradiation field. Most patients respond to clinical treatment with corticosteroids. Here, we describe a 47-year-old patient with cervical carcinoma, FIGO stage IIB, submitted to external beam radiotherapy and concomitant chemotherapy with cisplatin (40 mg/m2 weekly), followed by intracavitary brachytherapy. One month after the end of radiotherapy and chemotherapy, the patient underwent laparoscopic completion hysterectomy plus bilateral salpingo-oophorectomy, followed by three cycles of cisplatin 50 mg/m2 D1 and gemcitabine 1,000 mg/m2 D1 and D8. Four months after the surgery, she presented with a suspicious mass in the vaginal dome that proved to be an exuberant inflammatory reaction that regressed after treatment with corticosteroids.
- Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status(2023) FREITAS, Daniela de; AGUIAR, Fernando Nalesso; ANTON, Cristina; ALMEIDA, Danielle Cristina de; BACCHI, Carlos Eduardo; CARVALHO, Jesus Paula; CARVALHO, Filomena MarinoDNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to mi-crosatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid his-tology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less & GE;50% myometrial inva-sion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myo-metrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.
- Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report(2024) GOMES, Luciana Beatriz Mendes; SANDOVAL, Renata Lazari; XAVIER, Camila Braganca; CORREA, Tatiana Strava; MATUDA, Raquel Midori Koga; SOUZA, Zenaide Silva de; LIMA, Luiz Guilherme Cernaglia Aureliano de; MACEDO, Mariana Petaccia de; CARVALHO, Filomena Marino; SUZUKI, Daniele AssadMalignant mixed mullerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease's molecular features and possible therapeutic approaches.