CRISTINA ANTON
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Clinical treatment of vulvar Paget's disease: a case report(2011) ANTON, Cristina; LUIZ, Arthur Vicentini da Costa; CARVALHO, Filomena Marino; BARACAT, Edmund Chada; CARVALHO, Jesus Paula
- A novel model to estimate lymph node metastasis in endometrial cancer patients(2017) ANTON, Cristina; SILVA, Alexandre Silva e; BARACAT, Edmund Chada; DOGAN, Nasuh Utku; KOHLER, Christhardt; CARVALHO, Jesus Paula; FAVERO, Giovanni Mastrantonio diOBJECTIVES: To evaluate the postoperative pathological characteristics of hysterectomy specimens, preoperative cancer antigen (CA)-125 levels and imaging modalities in patients with endometrial cancer and to build a risk matrix model to identify and recruit patients for retroperitoneal lymphadenectomy. METHODS: A total of 405 patients undergoing surgical treatment for endometrial cancer were retrospectively reviewed and analyzed. Clinical (age and body mass index), laboratory (CA-125), radiological (lymph node evaluation), and pathological (tumour size, grade, lymphovascular space invasion, lymph node metastasis, and myometrial invasion) parameters were used to test the ability to predict lymph node metastasis. Four parameters were selected by logistic regression to create a risk matrix for nodal metastasis. RESULTS: Of the 405 patients, 236 (58.3%) underwent complete pelvic and para-aortic lymphadenectomy, 96 (23.7%) underwent nodal sampling, and 73 (18%) had no surgical lymph node assessment. The parameters predicting nodal involvement obtained through logistic regression were myometrial infiltration > 50%, lymphovascular space involvement, pelvic lymph node involvement by imaging, and a CA-125 value > 21.5 U/mL. According to our risk matrix, the absence of these four parameters implied a risk of lymph node metastasis of 2.7%, whereas in the presence of all four parameters the risk was 82.3%. CONCLUSION: Patients without deep myometrial invasion and lymphovascular space involvement on the final pathological examination and with normal CA-125 values and lymph node radiological examinations have a relatively low risk of lymph node involvement. This risk assessment matrix may be able to refer patients with high-risk parameters necessitating lymphadenectomy and to decide the risks and benefits of lymphadenectomy.
- A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses(2012) ANTON, Cristina; CARVALHO, Filomena Marino; OLIVEIRA, Elci Isabel; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund Chada; CARVALHO, Jesus PaulaOBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.
- L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion(2018) FREITAS, Daniela de; AGUIAR, Fernando Nalesso; ANTON, Cristina; BACCHI, Carlos Eduardo; CARVALHO, Jesus Paula; CARVALHO, Filomena MarinoBackground Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. Materials and methods We studied 47 consecutive patients aged 37-88 (61.34 +/- 10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. Results LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. Conclusions L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.
- Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes(2020) ANTON, Cristina; KLEINE, Rodolpho Truffa; MAYERHOFF, Eric; DIZ, Maria del Pilar Esteves; FREITAS, Daniela de; CARVALHO, Heloisa de Andrade; CARVALHO, Joao Paulo Mancusi de; SILVA, Alexandre Silva e; GENTA, Maria Luiza Nogueira Dias; SILVA, Andre Lopes de Faria e; SALIM, Rafael Calil; ARANHA, Andrea; LOPEZ, Rossana Veronica Mendoza; CARVALHO, Filomena Marino; BARACAT, Edmund Chada; CARVALHO, Jesus PaulaFew reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian institution over a 10-year period. This retrospective study included 703 patients diagnosed with endometrial cancer who were treated at a public academic tertiary hospital between 2008 and 2018. The following parameters were analyzed: age at diagnosis, race, body mass index, serum CA125 level before treatment; histological type and grade, and surgical stage. Outcomes were reported relative to histological type, surgical staging, serum CA125, lymph-vascular space involvement (LVSI), and lymph-node metastasis. The median patient age at diagnosis was 63 (range, 27-93) years (6.4% were < 50 years). Minimally invasive surgeries were performed in 523 patients (74.4%). Regarding histological grade, 468 patients (66.5%) had low-grade endometrioid histology and 449 patients (63.9%) had stage I tumors. Tumors exceeded 2.0 cm in 601 patients (85.5%). Lymphadenectomy was performed in 551 cases (78.4%). LVSI was present in 208 of the patients' tumors (29.5%). Ninety-three patients (13.2%) had recurrent tumors and 97 (13.7%) died from their malignant disease. The robust prognostic value of FIGO stage and lymph node status were confirmed. Other important survival predictors were histological grade and LVSI [overall survival: hazard ratio (HR) = 3.75, p < 0.001 and HR = 2.01, p = 0.001; recurrence: HR = 2.49, p = 0.004 and HR = 3.22, p = 0.001, respectively). Disease-free (p = 0.087) and overall survival (p = 0.368) did not differ significantly between patients with stage II and III disease. These results indicate that prognostic role of cervical involvement should be explored further. This study reports the characteristics and outcomes of endometrial cancer in a large population from a single institution, with systematic surgical staging, a predominance of minimally invasive procedures, and well-documented outcomes. Prognostic factors in the present study population were generally similar to those in other countries, though our patients' tumors were larger than in studies elsewhere due to later diagnosis. Our unexpected finding of similar prognoses of stage II and III patients raises questions about the prognostic value of cervical involvement and possible differences between carcinomas originating in the lower uterine segment versus those originating in the body and fundus. The present findings can be used to guide public policies aimed at improving the diagnosis and treatment of endometrial cancer in Brazil and other similar countries.
- Surgical treatment of endometrial cancer in developing countries: reasons to consider systematic two-step surgical treatment(2015) ANTON, Cristina; FAVERO, Giovanni Mastrantonio di; KOEHLER, Christhardt; CARVALHO, Filomena Marino; BARACAT, Edmund Chada; CARVALHO, Jesus PaulaOBJECTIVE : The aim of this study was to determine the lymph node status in a large cohort of women with endometrial cancer from the public health system who were referred to an oncology reference center in Brazil to identify candidates for the omission of lymphadenectomy based on clinicopathological parameters. METHODS : We retrospectively analyzed a cohort of 310 women with endometrial cancer (255 endometrioid, 40 serous, and 15 clear cell tumors) treated between 2009 and 2014. We evaluated the histological type, grade (low vs. high), tumor size (cm), depth of myometrial invasion (<= 50%, > 50%) and lymphovascular space invasion to determine which factors were correlated with the presence of lymph node metastasis. RESULTS : The factors related to lymph node involvement were tumor size (p =0.03), myometrial invasion (p < 0.01), tumor grade (p < 0.01), and lymphovascular space invasion (p < 0.01). The histological type was not associated with the nodal status (p = 0.52). Only twelve of 176 patients (6.8%) had low-grade endometrioid carcinoma, tumor size <= 2 cm and < 50% myometrial infiltration. CONCLUSIONS : The omission of lymphadenectomy based on the histological type, grade, tumor size and depth of myometrial invasion is not likely to have a large impact on the surgical treatment of endometrial cancer in our population because most patients present with large and advanced tumors. New strategies are proposed that prioritize hysterectomy performed in a general hospital as soon as possible after diagnosis, followed by an evaluation of the need for lymph node dissection at a reference center.
- 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.
- Introduction of robotic surgery for endometrial cancer into a Brazilian cancer service: a randomized trial evaluating perioperative clinical outcomes and costs 6061/clinics/2017/e522s(2018) SILVA, Alexandre Silva e; CARVALHO, Joao Paulo Mancusi de; ANTON, Cristina; FERNANDES, Rodrigo Pinto; BARACAT, Edmund Chada; CARVALHO, Jesus PaulaOBJECTIVE: The purpose of this study was to evaluate the clinical outcome and costs after the implementation of robotic surgery in the treatment of endometrial cancer, compared to the traditional laparoscopic approach. METHODS: In this prospective randomized study from 2015 to 2017, eighty-nine patients with endometrial carcinoma that was clinically restricted to the uterus were randomized in robotic surgery (44 cases) and traditional laparoscopic surgery (45 cases). We compared the number of retrieved lymph nodes, total time of surgery, time of each surgical step, blood loss, length of hospital stay, major and minor complications, conversion rates and costs. RESULTS: The ages of the patients ranged from 47 to 69 years. The median body mass index was 31.1 (21.4-54.2) in the robotic surgery arm and 31.6 (22.9-58.6) in the traditional laparoscopic arm. The median tumor sizes were 4.0 (1.5-10.0) cm and 4.0 (0.0-9.0) cm in the robotic and traditional laparoscopic surgery groups, respectively. The median total numbers of lymph nodes retrieved were 19 (3-61) and 20 (4-34) in the robotic and traditional laparoscopic surgery arms, respectively. The median total duration of the whole procedure was 319.5 (170-520) minutes in the robotic surgery arm and 248 (85-465) minutes in the traditional laparoscopic arm. Eight major complications were registered in each group. The total cost was 41% higher for robotic surgery than for traditional laparoscopic surgery. CONCLUSIONS: Robotic surgery for endometrial cancer presented equivalent perioperative morbidity to that of traditional laparoscopic surgery. The duration and total cost of robotic surgery were higher than those of traditional laparoscopic surgery.