Browsing by Author "Castillo, Miluska"

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A biomarker study in Peruvian males with breast cancer
(Baishideng Publishing Group, 2021) Castaneda, Carlos; Castillo, Miluska; Bernabe, LA; Sanchez, J; Torres, E; Suarez, N; Tello, K; Fuentes, H; Dunstan, J; De La Cruz, M; Cotrina, JM; Abugattas, J; Guerra, H; Gomez, HL
AIM:To investigate clinicopathological features and biomarkers of BC tumors in males and their prognostic value in Peruvian population. METHODS: This study looked at a single-institution series of 54 Peruvian males with invasive BC who were diagnosed from Jan 2004 to June 2018. Standard pathological features, TIL levels, MMR proteins, AR immunohistochemistry staining, and PIK3CA gene mutations were prospectively evaluated in cases with available paraffin material. Percentage of AR and estrogen receptor (ER) positive cells was additionally calculated by software after slide scanning. Statistical analyses included association tests, intraclass correlation test and Kaplan Meier overall survival curves. RESULTS: The median age was 63 years and most cases were ER-positive (85.7%), HER2 negative (87.2%), Luminal-A phenotype (60%) and clinical stage II (41.5%) among our male breast tumors. Median TIL was 10% and higher levels tended to be associated with Luminal-B phenotype and higher grade. AR-positive was found in 85.3% and was correlated with ER (intraclass index of 0.835, P < 0.001). Loss of MMR proteins was found in 15.4% and PIK3CA mutation (H1047R) in 14.3% (belonged to the Luminal-A phenotype). Loss of MMR proteins was associated with AR-negative (P = 0.018) but not with ER (P = 0.43) or TIL (P = 0.84). Early stages (P < 0.001) and lower grade (P = 0.006) were associated with longer overall survival. ER status, phenotype, AR status, TIL level, MMR protein loss nor PIK3CA mutation was not associated with survival (P > 0.05). CONCLUSION: Male BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.
Concurrent Detection of Circulating Tumor Cells and Circulating Tumor DNA in Triple-negative Breast Cancer
(Asian Pacific Journal of Cancer Care, 2021) Gomez, Henry L.; Castaneda, Carlos A.; Castillo, Miluska; Reuben, James; Gao, Hui; Suarez, Nnacy; Bernabe, Luis A.; Cotrina, Jose M.; Dunstan, Jorge; Velarde, Marco; Abugattas, Julio; Guerra, Henry
Objective: Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) provide tumor information in breast cancer. Our objective was to characterize CTCs, and contrasted them with ctDNA PIK3CA mutation in 24 triple-negative breast cancer (TNBC). Methods: CTCs genes were characterized by AdnaTest protocol and ctDNA by digital PCR. Results: We found CTCs genes in 37.5% and ctDNA PIK3CA mutations in 29.16%. Three cases with CTCs genes had concurrent ctDNA PIK3CA mutations. MUC1 or GA733-2 were found in 4 cases, and 3 of them had concurrent ctDNA PIK3CA. CTCs ALDH1/TWIST1 were found in 2 cases, AKT2 in one and PI3Kα in another, and none had concurrent ctDNA PIK3CA mutations. There was no correlation between CTCs and ctDNA detection. All 3 cases with CTC & cDNA concurrent finding underwent death during follow-up. Conclusion: Infrequent concurrent detection of CTC and ctDNA presence suggests that both represent independent processes in TNBC patients, and could identify worst prognosis cases.
Concurrent Detection of Circulating Tumor Cells and Circulating Tumor DNA in Triple-negative Breast Cancer
(Asian Pacific Journal of Cancer Care, 2021) Gomez, Henry L.; Castaneda, Carlos A.; Castillo, Miluska; Reuben, James; Gao, Hui; Suarez, Nnacy; Bernabe, Luis A.; Cotrina, Jose M.; Dunstan, Jorge; Velarde, Marco; Abugattas, Julio; Guerra, Henry
Objective: Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) provide tumor information in breast cancer. Our objective was to characterize CTCs, and contrasted them with ctDNA PIK3CA mutation in 24 triple-negative breast cancer (TNBC). Methods: CTCs genes were characterized by AdnaTest protocol and ctDNA by digital PCR. Results: We found CTCs genes in 37.5% and ctDNA PIK3CA mutations in 29.16%. Three cases with CTCs genes had concurrent ctDNA PIK3CA mutations. MUC1 or GA733-2 were found in 4 cases, and 3 of them had concurrent ctDNA PIK3CA. CTCs ALDH1/TWIST1 were found in 2 cases, AKT2 in one and PI3Kα in another, and none had concurrent ctDNA PIK3CA mutations. There was no correlation between CTCs and ctDNA detection. All 3 cases with CTC & cDNA concurrent finding underwent death during follow-up. Conclusion: Infrequent concurrent detection of CTC and ctDNA presence suggests that both represent independent processes in TNBC patients, and could identify worst prognosis cases.
Critical review of axillary recurrence in early breast cancer
(Elsevier Ireland Ltd, 2018) Castaneda, Carlos; Rebaza, P; Castillo, Miluska; Gomez, HL; De La Cruz, M; Calderon, G; Dunstan, J; Cotrina, JM; Abugattas, J; Vidaurre, T
Around 2% of early breast cancer cases treated with axillary lymph node dissection (ALND) underwent axillary recurrence (AR) and it has a deleterious effect in prognosis. Different scenarios have incorporated Sentinel Lymph Node (SLN) Biopsy (SLNB) instead of ALND as part of the standard treatment and more effective systemic treatment has also been incorporated in routine management after first curative surgery and after regional recurrence. However, there is concern about the effect of SLNB alone over AR risk and how to predict and treat AR. SLN biopsy (SLNB) has been largely accepted as a valid option for SLN-negative cases, and recent prospective studies have demonstrated that it is also safe for some SLN-positive cases and both scenarios carry low AR rates. Different studies have identified clinicopathological factors related to aggressiveness as well as high-risk molecular signatures can predict the development of locoregional recurrence. Other publications have evaluated factors affecting prognosis after AR and find that time between initial treatment and AR as well as tumor aggressive behavior influence patient survival. Retrospective and prospective studies indicate that treatment of AR should include local and systemic treatment for a limited time.
Detection of Helicobacter pylori in gastric cancer tissue through histopathology, immunohistochemistry and real-time reverse transcription-PCR
(Publmed, 2020) Castaneda, Carlos A; Castillo, Miluska; Sanchez, Joselyn; Casavilca, Sandro; Sanchez, Juvenal; Bernabe, Luis A; Suarez, Nancy; Chavez, Ivan; Ruiz, Eloy; Tello, Katherine; Villa, Maria R; Zevallos, Rocio; Montenegro, Paola; Dias-Neto, Emmanuel; Landa-Baella, Maria; Taxa, Luis
Aim:Helicobacter pylori is usually detected based on hematoxylin-eosin (H-E) features, but, immunohistochemistry (IHC) and real-time PCR (RT-PCR) are more precise in chronic-gastritis. We evaluated the relevance of these tests in Peruvian gastric cancer samples. Materials & methods: We performed and evaluated H-E, IHC staining and RT-PCR in 288 gastric tumors. Slides were independently evaluated by three pathologists. Results:H. pylori was detected in 167/287 through H-E, 140/288 through IHC and 175/288 through RT-PCR, and positive-status were associated (p < 0.001). H. pylori detection by H-E had a good concordance with IHC (kappa index = 0.632) but poor with RT-PCR (kappa index = 0.317). Higher median gene-copies were found in high H. pylori density through H-E or IHC (p < 0.001). Conclusion: H-E evaluation is accurate in gastric cancer, and IHC and RT-PCR can complement its results.
Distribution of tumor-infiltrating immune cells in glioblastoma
(Future Medicine Ltd., 2018) Orrego Puelles, Enrique,; Castaneda, Carlos A; Castillo, Miluska; Bernabe, LA; Casavilca, Sandro; Chakravarti, A; Meng, W; Garcia-Corrochano, Pamela; Villa-Robles, MR; Zevallos, R; Mejia, O; Deza, Pedro; Belmar-Lopez; Ojeda, CL
Aim: Evaluation of features related to infiltrating immune cell level in glioblastoma. Methods: Tumor-infiltrating lymphocytes (TILs) through H&E staining, and TILs (CD3, CD4, CD8 and CD20) and macrophage (CD68 and CD163) levels through immunohistochemistry were evaluated through digital analysis. Results: CD68 (9.1%), CD163 (2.2%), CD3 (1.6%) and CD8 (1.6%) had the highest density. Higher CD4+ was associated with unmethylated MGMT (p = 0.016). Higher CD8+ was associated with larger tumoral size (p = 0.027). Higher CD163+ was associated with higher age (p = 0.044) and recursive partitioning analysis = 4. Women (p < 0.05), total resection (p < 0.05), MGMT-methylation (p < 0.001), radiotherapy (p < 0.001), chemotherapy (p < 0.001) and lower CD4+ (p < 0.05) were associated with longer overall survival. Conclusion: Macrophages are more frequent than TILs. Some subsets are associated with clinical features.
Glioblastoma of pineal region: report of four cases and literature review
(Future Medicine Ltd., 2017) Orrego Puelles, Enrique; Casavilca Sambrano, Sandro; Garcia-Corrochano, Pamela; Rojas-Meza, S; Castillo, Miluska; Castaneda, Carlos A
We report four cases of glioblastoma in the pineal region. The patients presented a severe headache and vomiting. Brain imaging showed a heterogeneously enhanced tumor in the pineal region with obstructive hydrocephalus. Case 3 developed a subependymal dissemination. The patient went to ventricular-peritoneal shunt and subtotal or total resection and radiotherapy with/without chemotherapy. Cases 1 and 2 received radiation and died 8 and 11 later months. Cases 3 and 4 completed radiotherapy and chemotherapy, and survived 28 and 31 months after the initial diagnosis. Glioblastoma in the pineal region carry a poor prognosis and require neurooncology teams.
Latin American Study of Hereditary Breast and Ovarian Cancer LACAM: A Genomic Epidemiology Approach
(Publmed, 2019) Oliver, Javier; Quezada Urban, Rosalía; Franco Corté, Claudia Alejandra; Díaz Velásquez, Clara Estela; Montealegre Paez, Ana Lorena; Pacheco-Orozco, Rafael Adrián; Castro Rojas , Carlos; García-Robles, Reggie; López Rivera, Juan Javier; Gaitán Chaparro , Sandra; Milena Gómez, Ana; Suarez Obando, Fernando; Giraldo, Gustavo; Maya , Maria Isabel; Hurtado-Villa, Paula; Sanchez, Ana Isabel; Serrano , Norma; Orduz Galvis , Ana Isabel; Aruachan, Sandra; Nuñez Castillo, Johanna; Frecha, Cecilia; Riggi, Cecilia; Jauk, Federico; Gómez García, Eva María; Carranza, Claudia Lorena; Zamora, Vanessa; Torres Mejía, Gabriela; Romieu, Isabelle; Castañeda, Carlos Arturo; Castillo, Miluska; Gitler, Rina; Antoniano, Adriana; Rojas Jiménez, Ernesto; Romero Cruz, Luis Enrique; Vallejo Lecuona, Fernando; Delgado Enciso, Iván; Martínez Rizo, Abril Bernardette; Flores Carranza, Alejandro; Benites Godinez, Verónica; Méndez Catalá, Claudia Fabiola; Herrera, Luis Alonso; Irasema Chirino, Yolanda; Terrazas, Luis Ignacio; Perdomo, Sandra; Vaca Paniagua , Felipe
Purpose: Hereditary Breast and Ovarian Cancer (HBOC) syndrome is responsible for ~5-10% of all diagnosed breast and ovarian cancers. Breast cancer is the most common malignancy and the leading cause of cancer-related mortality among women in Latin America (LA). The main objective of this study was to develop a comprehensive understanding of the genomic epidemiology of HBOC throughout the establishment of The Latin American consortium for HBOC-LACAM, consisting of specialists from 5 countries in LA and the description of the genomic results from the first phase of the study. Methods: We have recruited 403 individuals that fulfilled the criteria for HBOC from 11 health institutions of Argentina, Colombia, Guatemala, Mexico and Peru. A pilot cohort of 222 individuals was analyzed by NGS gene panels. One hundred forty-three genes were selected on the basis of their putative role in susceptibility to different hereditary cancers. Libraries were sequenced in MiSeq (Illumina, Inc.) and PGM (Ion Torrent-Thermo Fisher Scientific) platforms. Results: The overall prevalence of pathogenic variants was 17% (38/222); the distribution spanned 14 genes and varied by country. The highest relative prevalence of pathogenic variants was found in patients from Argentina (25%, 14/57), followed by Mexico (18%, 12/68), Guatemala (16%, 3/19), and Colombia (13%, 10/78). Pathogenic variants were found in BRCA1 (20%) and BRCA2 (29%) genes. Pathogenic variants were found in other 12 genes, including high and moderate risk genes such as MSH2, MSH6, MUTYH, and PALB2. Additional pathogenic variants were found in HBOC unrelated genes such as DCLRE1C, WRN, PDE11A, and PDGFB. Conclusion: In this first phase of the project, we recruited 403 individuals and evaluated the germline genetic alterations in an initial cohort of 222 patients among 4 countries. Our data show for the first time in LA the distribution of pathogenic variants in a broad set of cancer susceptibility genes in HBOC. Even though we used extended gene panels, there was still a high proportion of patients without any detectable pathogenic variant, which emphasizes the larger, unexplored genetic nature of the disease in these populations.
Level of tumor-infiltrating lymphocytes and density of infiltrating immune cells in different malignancies
(Publmed, 2019) Castañeda, Carlos A.; Castillo, Miluska; Aliaga, Karina; Bernabé, Luis A.; Casavilca, Sandro; Sánchez, Joselyn; Torres-Cabala, Carlos A.; Gómez , Henry L.; Mas, Luis; Dunstan, Jorge; Cotrina, José M; Abugattas, Julio; Chávez, Iván; Ruiz, Eloy; Montenegro, Paola; Rojas, Víctor; Orrego, Enrique; Gálvez-Nino, Marco; Félix , Brayam; Landa-Baella, María P.; Vidaurre, Tatiana; Villa, María R; Zevallos, Rocío; Taxa, Luis; Guerra, Henry; Jorge Luis
Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.
Prevalence of H. pylori Infection in Relatives of Peruvian Patients with Gastric Cancer
(Asian Pacific Journal of Cancer Care, 2021) Castillo, Miluska; Bernabe, Luis A.; Castaneda, Carlos A.; Suarez, Nancy; Barreda, Fernando; Valdivia, Daniel; Ruiz, Eloy; Nieves, Jais; Dias-Neto, Emmanuel; Landa-Baella, Maria; Montano-Flores, Jennifer; Chavez, Ivan
bjective: The aim of this study was to determine the relationship between Helicobacter pylori (H. pylori) infection in relatives and patients with gastric cancer (GC). Methods: H. pylori infection was evaluated by the breath urease test in 171 relatives and by qPCR technique in gastric tissue of 61 patients (n=45 for GC and n=16 for non-GC). Results: There were included 137 relatives of GC patients and 34 of non-GC. The median age of the relatives of patients with a gastric tissue sample was 39 years (10-86). Infection was found in 60.2% (n=103) relatives. There were no higher H. pylori infection rates in relatives of patients with gastric cancer (62% vs 62.9%, p=0.33), H. pylori infection (60% vs 60%, p=0.96), or metaplasia (58.8% vs 61.8%, p=0.71). Conclusion: The prevalence of infection in relatives of GC patients is high in our population but not associated with H. pylori presence in the paired case
Prevalence of Helicobacter pylori Infection, Its Virulent Genotypes, and Epstein-Barr Virus in Peruvian Patients With Chronic Gastritis and Gastric Cancer
(American Society of Clinical Oncology, 2019) Castaneda, Carlos; Castillo, Miluska; Chavez, I; Barreda, F; Suarez, N; Nieves, J; Bernabe, LA; Valdivia, D; Ruiz, E; Dias-Neto, E; Landa-Baella, MP; Bazan, Y; Rengifo, CA; Montenegro, P
Purpose: Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. Patients and methods: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. Results: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC (P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate (P < .001) and multivariate (P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. Conclusion: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.
Prognostic factors for patients with newly diagnosed brain metastasis from breast cancer
(Future Medicine Ltd., 2015) Castaneda, Carlos; Flores, R; Castillo, Miluska; Rojas, KY; Castillo, M; Dolores-Cerna, K; Flores, C; Belmar-Lopez, C; Milla, E; Gomez, HL
Aim: This retrospective study determined features associated with brain metastasis (BM) in women with breast cancer. Patients & methods: A total of 215 initially early breast cancer cases were included. We reviewed files and CT scan images of BM. Results: Median age was 47 years and most of our cases were stage III (58.6%), grade III (62.8%), ER negative (62.3%) and nonluminal (59.1%). Median survival after BM was 4 months. Nonluminal, extracranial disease, time to CNS shorter than 15 months, >three brain lesions and poor breast-graded prognostic assessment and recursive partitioning analysis scores were associated with shorter survival. Adding extracranial disease to breast-graded prognostic assessment score also predicted survival after BM. Radiation response was assessed in 57 patients and response tended to be associated with nonluminal phenotype but not with survival. Conclusion: Factors associated with both initial tumor and clinical features at BM time are associated with shorter survival in our Latinas population.
Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma
(Springer-Verlag Italia Srl, 2013) Castaneda, Carlos; Castillo, Miluska; Torres-Cabala, C; Bernabe, LA; Casavilca, S; Villegas, V; Sanchez, J; de la Cruz, M; Dunstan, J; Cotrina, JM; Gomez, HL; Chavez, C; Landa-Baella, MP; Tello, K; Felix, BF; Abugattas, J
Purpose: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis.
Role of undifferentiation markers and androgen receptor expression in triple-negative breast cancer
(Wiley-Blackwell Publishing Ltd, 2019) Castaneda, Carlos; Castillo, Miluska; Enciso, JA; Enciso, N; Bernabe, LA; Sanchez, J; Guerra, H; Chavez, C; Landa-Baella, M; De-La-Cruz M; Villa-Robles, M; Tello, K; Gomez, HL
No abstract available
Tuberculosis That Mimics Cancer: Cases Referred to the National Institute of Neoplastic Diseases, Lima-Peru
(Instituto Nacional de Salud, 2018) Villena-Suarez, JR; Vicente, W; Taxa Rojas, Luis; Cuéllar PL, Luís; Nuñez-Butrón, MT; Villegas, V; Castillo, Miluska; Castaneda, Carlos A
Tuberculosis (TB) is a major public health problem that, due to the clinical variability of its presentation, can be confused with cancer. The aim of this study was to identify the clinical-radiological characteristics and to describe the methodology that allowed to achieve a TB diagnosis in patients referred to the National Institute of Neoplastic Diseases (INEN) with a presumed diagnosis of cancer between 2014 and 2016. The study included 170 patients (52.4% men) with an average age of 41.1 years; 18% presented a history of contact with TB, and 5.9% had had the disease previously. The TB was pulmonary in 22.4% and extrapulmonary in 77.7% of patients. The most frequent symptoms were respiratory, tumor, weight loss, and neurological. The cancer diagnoses most frequently discarded were lymphoma, lung cancer, and brain cancer. The lesions that suggested a neoplasm indicated an advanced clinical stage in 63.5%. Therefore, it follows that the symptoms and images associated with TB can be confused with malignant neoplasms.