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Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda miluska castillo Luis A Bernabe Joselyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz Juvenal Sanchez Fernando Barreda Daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio J Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

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Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy

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World Journal of Clinical Oncology 2018年第2期9卷 33-41页

作者： Marco Galvez Carlos A Castaneda Joselyn Sanchez miluska castillo Lia Pamela Rebaza Gabriela Calderon Miguel De La Cruz Jose Manuel Cotrina Julio Abugattas Jorge Dunstan Henry Guerra Omar Mejia Henry L Gomez Department of Medical Oncology Instituto Nacional de Enfermedades Neoplasicas Faculty of Medicine Universidad Peruana San Juan Bautista Department of Research Instituto Nacional de Enfermedades Neoplasicas Department of Breast Cancer Surgery Instituto Nacional de Enfermedades Neoplasicas Department of Pathology Instituto Nacional de Enfermedades Neoplasicas

AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001),

关键词： Breast cancer Subtype Tumor-infiltrating lymphocytes Neoadjuvant therapy Pathological complete response Survival

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Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy

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World Journal of Clinical Oncology 2016年第5期7卷 387-394页

作者： Carlos A Castaneda Elizabeth Mittendorf Sandro Casavilca Yun Wu miluska castillo Patricia Arboleda Teresa Nunez Henry Guerra Carlos Barrionuevo Ketty Dolores-Cerna Carolina Belmar-Lopez Julio Abugattas Gabriela Calderon Miguel De La Cruz Manuel Cotrina Jorge Dunstan Henry L Gomez Tatiana Vidaurre Department of Research Instituto Nacional de Enfermedades Neoplasicas Department of Medical Oncology Instituto Nacional de Enfermedades Neoplasicas Department of Surgical Oncology the University of Texas MD Anderson Cancer Center Department of Pathology Instituto Nacional de Enfermedades Neoplasicas Department of Pathology Division of Pathology the University of Texas MD Anderson Cancer Center Department of Breast Cancer Surgery Instituto Nacional de Enfermedades Neoplasicas

AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays(TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P = 0.0251) and outcome(P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. PostNAC lesions with pC R had similar TIL levels than those without pCR(P = 0.6331). NAC produced a TIL decrease in full-face sections(P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS). Higher counts of CD3 in pre-NAC samples had longer overallsurvival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related.

关键词： Triple-negative breast cancer Survival Tumor-infiltrating lymphocytes Neoadjuvant therapy

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A biomarker study in Peruvian males with breast cancer

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World Journal of Clinical Oncology 2021年第10期12卷 926-934页

作者： Carlos A Castaneda miluska castillo Luis A Bernabe Joselyn Sanchez Ebert Torres Nancy Suarez Katherine Tello Hugo Fuentes Jorge Dunstan Miguel De La Cruz Jose Manuel Cotrina Julio Abugattas Henry Guerra Henry L Gomez Faculty of Health Sciences Universidad Cientifica del SurLima 15067Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Breast Cancer Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru

BACKGROUND Breast cancer(BC)frequency in males is extremely low and tumor features vary from its female counterpart.Breast cancer clinical and pathological features differ by race in women.Tumor infiltrating lymphocyte(TIL)levels,mismatch repair(MMR)protein loss,androgen receptor(AR)expression,and PIK3CA gene mutations are predictive biomarkers of response to biological therapy in female BC.There is limited information about clinical and pathological features as well as predictive biomarkers in males of non-Caucasian races with BC.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,P0.05).CONCLUSION Male BC is usu

关键词： Male breast neoplasm Androgen receptor Tumor-infiltrating lymphocyte Mismatch repair protein PIK3CA mutation

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Nodal involvement and p16-staining in upper alveolar ridge and hard palate cancer

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 186-198页

作者： Edgar Salas Pedro Sanchez Juan Postigo Carlos A.Castaneda miluska castillo Valeria Villegas Luis Cano Sandro Casavilca Luis A.Bernabe Carolina Belmar Maria R.Villa-Robles Raul Mantilla Henry Guerra Head&Neck Surgery Department Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Research Department Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Medicine Universidad Peruana San Juan BautistaLima 15067Peru Pathology Department Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru

Aim:Upper alveolar ridge and hard palate squamous cancer is an infrequent malignancy.We evaluated factors associated with neck involvement and with p16-staining.Methods:Head and neck squamous-cell carcinoma(SCC)patients who went to Head and Neck Department between 1997 and 2011 were screened,and 73 resected upper alveolar ridge and 5 hard palate SCC were selected.Tumors with available tissue were stained with p16 immunohistochemistry.Results:Median age was 64.4 years,55.1%were female,and 73.1%were in clinical stage IV.Neck dissections were performed in 24 and pathologically confirmed node metastases were found in 19(24.3%).Cervical recurrence was found in 18 patients(23.1%)and was associated with histological grade(P=0.037).Three(7.3%)of 41 lesions were positive for p16 and tended to be younger(P=0.067).Lymphovascular invasion was associated with shorter disease-free survival(DFS)(P=0.026)and overall survival(OS)(P=0.021).Larger cT(P=0.019),perineural invasion(P=0.039)and neck dissection(P=0.010)were associated with shorter OS.Neck node involvement tended to have shorter DFS(31%vs.48.7%,P=0.278)and OS(25.1%vs.48.5%,P=0.340),and neck recurrence tended to have shorter OS(9.3%vs.52.3%,P=0.064).Conclusion:Neck involvement and recurrence are frequent in this location.P16-positive cases were present in 7.3%and tended to be associated with younger age.

关键词： P16 head neck maxilla prognosis survival

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