Molecular classification of breast cancer using IHC markers: experience from a tertiary cancer center in south India

Background: Breast cancer is a very heterogeneous disease. Molecular or intrinsic subtypes of breast cancer are based on the gene expression profiling. Doing gene expression profiling in each case is practically difficult. So most of the labs depend on immunohistochemistry to classify breast tumors into various molecular-like subtypes. In this study, we have used immune histochemistry to classify tumors into various subtypes. Methods: We have retrospectively collected the data of breast cancer patients treated at Apollo Cancer Center, Chennai, in whom ER, PR, HER 2 Neu and Ki 67 were done, and the data was analyzed. Results: The commonest molecular subtype observed in the present study was Luminal B HER2 positive, constituting 40% of the cases, followed by a HER2 positive (non-luminal) subtype in 20% of cases. The triple negative subtype was the third most frequent, comprising 18% of the cases. The least frequent subtype was Luminal A, seen in only 8% of cases. Conclusions: There is a higher proportion of luminal B HER2 positive and triple negative subtypes in our study population compared to the other studies in published literature. The proportion of luminal A was lesser in our study compared to the literature.

The immunohistochemical Galectin-3 expression in tumor and cancer-associated fibroblasts in invasive ductal carcinomas of breast and their relationship with clinicopathological parameters

Background: Galectin-3 has an important role in metastasis, therefore, Galectin-3-focused therapies have attracted attention for various cancers. Aim: We aimed to reveal the relationship between the expression of Galectin-3 within the tumor/cancer-associated fibroblasts (CAF) and clinicopathological parameters in patients with invasive ductal carcinomas. Materials and Methods: Hematoxylin and eosin-stained slides of breast excision materials diagnosed between 2010 and 2016 were re-examined retrospectively. Accordingly, 118 cases (luminal group = 58, Human epidermal growth factor receptor 2 (HER2) group = 27, and triple-negative breast carcinoma group [TNBC] =33 cases) were included. Galectin-3 levels were evaluated with a calculated H-score in tumor and semiquantitatively in CAFs. Statistical Analysis: Data was analyzed with t-tests and Chi-square tests. Kaplan–Meier and Log-rank tests were used for survival analysis. Results: The presence of Galectin-3 expression in CAFs but not in the tumor was associated with the greater number of axillary metastatic nodes and advanced pN stage. The loss of Galectin-3 expression in CAFs was more frequent in TNBC. There was no significant relationship between the expression level of Galectin-3 and survival status. However, in most of the cases with distant metastasis or patients who died, Galectin-3 was negative in the tumor, whereas it was positive in CAFs. Conclusions: The expression of Galectin-3 in tumors and CAFs may have a role in metastasis to axillary lymph nodes and distant sites. In terms of molecular subtype, TNBCs show a relationship with Galectin-3 negativity in CAFs.

Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material & Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Identification of senescence-related molecular subtypes and key genes for prostate cancer / 亚洲男科学杂志(英文版)

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.

Progress of pathological classification in evaluating the prognosis of diffuse large B-cell lymphoma / 白血病·淋巴瘤

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with significant invasive and heterogeneous pathological morphology and clinical manifestations. In recent years, genomic analysis has yielded different molecular profile subsets, thus explaining the heterogeneity of DLBCL and enabling personalized precision therapy. This review summarizes the complex biology of DLBCL and discusses the potential impact of pathological classification on precision therapy of DLBCL.

Molecular subtypes of invasive breast carcinoma of no special type, their correlation with histopathological features, Ki 67 index and tumor budding: A retrospective comparative study

Context: Tumor budding (TB), poorly differentiated clusters (PDCs), and Ki 67 index are proven adverse prognostic factors in breast carcinoma. Though the relation of Ki 67 index with molecular subtypes of breast carcinoma have been extensively studied, there is very limited information on the role of TB and PDCs. Aims: To grade TB, PDCs, and Ki 67 index and assess histological features and relationship of all these with molecular subtypes of invasive breast carcinoma of no special type. Methods and Material: Retrospective study of 148 cases from 1/1/2019 to 30/12/2019. Division of molecular groups – Luminal A, Luminal B, Her2 neu positive, and triple-negative breast carcinomas (TNBC), and Ki 67 index grades based on St Gallen criteria, intratumoral and peritumoral TB and PDC grades as per the International Tumor Budding Consensus Conference (ITBCC) criteria for colon and correlation between these and other histological features with the molecular subtypes were done. Statistical Analysis: Chi-square test, univariate and multivariate logistic regression models were used. Results: Significant correlation was seen between TB and lymphovascular emboli, Luminal B tumors with high-grade TB and PDCs, Her 2 neu positive and TNBC tumors with low-grade TB, circumscribed tumor margins, tumor necrosis, and Luminal B, Her 2 neu positive and TNBC tumors with larger tumor size and high nuclear grades.Conclusions: TB and PDCs are useful in the prognostication of Luminal A and B tumors when the Ki 67 index values are low/intermediate. Her 2 neu positive and TNBC tumors have a high nuclear grade with necrosis and no association with TB or PDCs.

Relación entre los factores estímulo estrogénicos y subtipos biológicos de cáncer de mama luminal A, luminal B y HER2 / Relationship between estrogenic stimulating factors and biological subtypes of luminal A, luminal B and HER2 breast cancer

Resumen ANTECEDENTES: El cáncer de mama es la principal neoplasia en incidencia y mortalidad en mujeres. Los subtipos moleculares: luminal A, luminal B, HER2 y triple negativo tienen un pronóstico y tasas de supervivencia diferentes. En la bibliografía está demostrada la estrecha asociación entre los factores estímulo estrogénicos y el cáncer de mama en general, aunque las diferencias no son claras debido a los subtipos moleculares. OBJETIVO: Revisar la bibliografía reciente y describir la relación entre los subtipos moleculares del cáncer de mama y los factores reproductivos. METODOLOGÍA: Búsqueda en las bases de datos PubMed y LILACS con los términos MeSH y DeCS: neoplasias de la mama, subtipos moleculares, factores de riesgo, factores reproductivos. Se buscó la asociación entre los antecedentes de paridad, edad al primer embarazo y el antecedente de lactancia materna con los subtipos moleculares de cáncer de mama: luminal A, luminal B y HER2. RESULTADOS: Se obtuvieron 366 artículos y se eliminaron 352 por: duplicidad en títulos y resúmenes, sin pertinencia para el tema, protocolos de investigación que no estudiaran la asociación entre factores estímulo estrogénicos con los subtipos moleculares de cáncer de mama. Al final, el análisis se hizo con 14 artículos. CONCLUSIONES: Los tumores con receptores hormonales positivos se asociaron con: edad mayor al primer embarazo, mayor tiempo entre la menarquia y el primer embarazo a término y edad avanzada en el último embarazo. Factores protectores para tumores luminales y HER2 puro: lactancia materna y multiparidad.

Abstract BACKGROUND: Breast cancer represents the main neoplasia in incidence and mortality in women, it can be divided into molecular subtypes (luminal A, luminal B, HER2 and triple negative) having a differential prognosis and survival rates. There is literature that demonstrates the strong association between estrogenic stimulating factors and breast cancer, but the existing differences by molecular subtypes are not clear. OBJECTIVE: To review the recent literature and describe the relationship found between molecular subtypes of breast cancer and estrogenic stimulating factors. METHODOLOGY: Search in the PubMed and LILACS databases with the MeSH and DeCS terms: breast neoplasms, molecular subtypes, risk factors, reproductive factors, looking for the association between the antecedents of parity, age at first pregnancy and history of breastfeeding with molecular subtypes of breast cancer (luminal A, luminal B and HER2). RESULTS: A total of 366 results were obtained, excluding 352 articles when evaluating duplicity, titles and abstracts, articles without relevance to the topic, research protocols and articles that did not study the association of estrogenic stimulating factors with molecular subtypes of breast cancer, resulting in 14 articles. CONCLUSIONS: Hormone receptor-positive tumors were found to be associated with older age at first pregnancy, longer time between menarche and first term pregnancy and older age at last pregnancy. Breastfeeding and multiparity were found as protective factors for luminal tumors and pure Her2.

Volumetric modulated arc radiosurgery for brain metastases from breast cancer: A single-center study / Radiocirugía con arcoterapia volumétrica modulada para el tratamiento de metástasis cerebrales de cáncer de mama: Un estudio monocéntrico

Abstract Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyse retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival comparable to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes, are factors that significantly influence patient survival.

Resumen Antecedentes: La radioterapia holocraneal (WBRT) y la radiocirugía estereotáctica (SRS) son dos modalidades de tratamiento comúnmente empleados para el tratamiento de las metástasis cerebrales (BMs). Objetivo: El propósito de este estudio es analizar de forma retrospectiva el control local y la supervivencia de los pacientes con BMs de cáncer de mama (BC) tratados mediante radiocirugía empleando arcoterapia volumétrica modulada (VMAT-RS). Métodos: Se analizaron 18 pacientes con 41 BMs de BC tratados mediante VMAT-RS. Se clasificaron según el subtipo molecular de BC y el GPA (Graded Prognostic Assessment) modificado de cáncer de mama. Los pacientes presentaron de 1-4 BMs, las cuales fueron tratadas con 5 arcos VMAT no coplanares. Se analizó la distribución espacial de las BMs, la influencia del status del receptor en la localización de las lesiones y la supervivencia evaluada mediante el modelo de Kaplan-Meier. Resultados: La mediana del tiempo de supervivencia (MST) fue de 19.7 meses. Se hallaron diferencias estadísticamente significativas en el MST según el índice de Karnofsky (p= 0.02) y el status de HER2 (p= 0.004), siendo más prolongado en las pacientes HER2+. Por último, nuestros resultados mostraron que el cerebelo es el lugar predominante de las BMs de cáncer de mama, y también sugirieron que las BMs HER2+ presentaban una predilección por algunas estructuras de la circulación posterior, como el cerebelo, el tronco cerebral y los lóbulos occipitales (p= 0.048). Conclusiones: VMAT-RS es una técnica con una supervivencia global comparable a otras técnicas de radiocirugía. La situación basal en el momento del tratamiento, el GPA modificado de cáncer de mama así como los subtipos moleculares de cáncer de mama, son factores que influyen de forma significativa en la supervivencia de los pacientes.

Identification of 5-methylcytosine-related signature for predicting prognosis in ovarian cancer

BACKGROUND: Ovarian cancer is one of the most common malignancies often resulting in a poor prognosis. 5-methylcytosine (m5C) is a common epigenetic modification with roles in eukaryotes. However, the expression and function of m5C regulatory factors in ovarian cancer remained unclear. RESULTS: Two molecular subtypes with different prognostic and clinicopathological features were identified based on m5C regulatory factors. Meanwhile, functional annotation showed that in the two subtypes, 452 differentially expressed genes were significantly related to the malignant progression of ovarian cancer. Subsequently, four m5C genes were screened to construct a risk marker predictive of overall survival and indicative of clinicopathological features of ovarian cancer, also the robustness of the risk marker was verified in external dataset and internal validation set. multifactorial cox regression analysis and nomogram demonstrated that risk score was an independent prognostic factor for ovarian cancer prognosis. CONCLUSIONS: In conclusion, our results revealed that m5C-related genes play a critical role in tumor progression in ovarian cancer. Further detection of m5C methylation could provide a novel targeted therapy for treating ovarian cancer.

Frecuencia de subtipos moleculares de cáncer de mama, Hospital Metropolitano, 2016-2019, Quito- Ecuador / Frequency of molecular subtypes of breast cancer, Hospital Metropolitano, 2016-2019, Quito- Ecuador

RESUMENObjetivo: Determinar el tipo molecular más común de CM en el Hospital Metropolitano. Metodología: Se realizó un estudio descriptivo, retrospectivo, en el cual se revisaron los informes histopatológicos de todos los casos de cáncer de mama diagnosticados desde el 01 de enero del 2016 al 31 de diciembre del 2019, teniendo en cuenta los datos inmunohistoquímicos para su clasificación. En el periodo estudiado se evidenció un total de 276 casos correspondientes a cáncer de mama, posterior a la aplicación de los criterios de inclusión se analizaron los datos de 147 pacientes. Resultados: La media anual de casos nuevos fue de 40 ± 6. La media de edad al diagnóstico fue de 60.9 ± 13 años. La mayoría de pacientes están en el rango de edad de 40 a 69 años con 101 casos (69%). La mayoría de casos fue de tipo Luminal B con un total de 85 casos, lo cual corresponde al 54%, la minoría fueron de tipo triple negativo con 11 casos (7%). La mayor parte de casos (71%) tienen elevada profileración tumoral determinada por el valor de Ki-67. Conclusiones: El subtipo molecular de cáncer de mama más común es el Luminal B, y el menos frecuente es el triple negativo. La mayoría de casos tienen alta proliferación determinada por el valor de Ki-67

ABSTRACTObjective: To determine the most common molecular type of breast cancer in the Hospital Metropolitano. Methodology: This was a retrospective descriptive study, in which the histopathological reports of all breast cancer cases diagnosed from January 1, 2016 to December 31, 2019 were reviewed, taking into account immunohistochemical data for classification. In the period studied, a total of 276 cases corresponding to breast cancer were evidenced, after clas-sifying individual criterias, data from 147 patients were analyzed. Results: The annual average of new cases was 40 ± 6. The average age at diagnosis was 60.9 ± 13 years. A large number of patients are in the age range of 40 to 69 years with 101 cases (69%). More than a half were Luminal B type with a total of 85 cases which corresponds to 54%, the minority were triple negative type with 11 cases (7%). The predominant number of cases (71%) have high tumor profiling determined by Ki-67. Conclusions: In this retrospective study we found that the most common molecular subtype of breast cancer is Luminal B, and the least frequent is triple negative. The results also demonstrate that most of the cases have high proliferation determined the value of Ki-67

Current research status and progress in comprehensive diagnosis and treatment of pancreatic cancer in the era of targeted therapy / 中华外科杂志

The incidence of pancreatic cancer (PC) has continuously shown an upward trend all over the world. It remains one of the most challenging malignant tumors in clinical practice and is characterized by difficult diagnosis in early stages, low surgical resection rate and poor prognosis. Due to its significant genetic heterogeneity, there are notable individual differences in disease progression, clinical efficacy, sensitivity to chemoradiotherapy, and prognosis among PC patients. In-depth study is needed to reveal the molecular biological characteristics of different PC subtypes and their correlation with clinical manifestations and chemoradiotherapy sensitivity, which could contribute to develop corresponding targeted therapeutic strategies.It is not only the fundamental basis for the innovation of PC morphological classification to molecular subtyping, but also a prerequisite for achieving a shift in treatment mode from "standard therapeutic strategy for different diseases" to "treat the same disease with different strategies" .This article reviews several hot issues on the comprehensive diagnosis and treatment of PC in the era of targeted therapy and prospects its future development.

Características imagenológicas de los carcinomas invasores de la mama según el subtipo molecular / Imaging characteristics of invasive carcinomas of the breast according to the molecular subtype

Introducción El cáncer de mama es una enfermedad heterogénea que comprende varios subtipos moleculares y perfiles genéticos. Dado que los cánceres de cada subgrupo tienen comportamiento similar, en la práctica clínica habitual se han definido cuatro subgrupos: Luminal A (la), Luminal B (lb), her2 positivo (her2) y Triple Negativo (tn). El conocimiento de los patrones de imágenes que se asocian a cada subgrupo es importante para poder predecir las características moleculares. Objetivos Describir, en una población hospitalaria, las características imagenológicas de los carcinomas invasores de la mama según los cuatro subtipos moleculares. Material y método Se realizó un estudio descriptivo de 167 cánceres de mama invasores (81 casos la, 45 lb, 24 tn y 17 her2) diagnosticados en el Servicio de Patología Mamaria del Hospital Provincial del Centenario que disponían del informe anatomopatológico con perfil inmunohistoquímico, mamografía y ecografía mamaria. Resultados La forma irregular del nódulo en mamografía fue la más frecuente en todos los subtipos, excepto en el tn, donde la forma oval fue más frecuente (p<0,0001). El margen espiculado fue más frecuente en los la (57,4%) y lb (47%); en el tn presentó mayor frecuencia el margen oscurecido (50%) y en el her2 el margen indistinto (41,6%) (p=0,004). La presencia de halo hiperecoico en ecografía fue más frecuente en los la (77%), en los lb (88%) y en los her2 (78.5%). En cambio, la interfaz abrupta fue más frecuente en el tn (100%) (p<0,0001). La forma irregular del nódulo en ecografía fue más observada en los la (90,5%), los lb (97,6%) y los her2 (100%), mientras que en el tn fue más frecuente la forma oval (60,8%) (p <0,0001). La orientación más frecuente del nódulo fue la no paralela para los la (89,1%), los lb (100%) y los her2 (92,8%) y la orientación paralela para el tn (65,2%) (p<0,0001). La presencia de vascularización fue más frecuente en los la (85,7%), los lb (86,2%) y los her2 (100%), siendo menos frecuente en el tn (20%) (p<0,0001). Conclusiones Los cánceres la y lb presentan similares características mamográficas y ecográficas. Los tumores her2 comparten muchas de estas características, a excepción de los márgenes en mamografía. En cambio, los tumores tn presentan características mamográficas y ecográficas diferentes a los otros subtipos moleculares, simulando lesiones benignas

Introduction Breast cancer is a heterogeneous disease that includes several molecular subtypes and genetic profiles. Since the cancers of each subgroup have similar behavior, in the usual clinical practice, four subgroups have been defined: Luminal A (la), Luminal B (lb), her2 positive (her2) and Triple Negative (tn). The knowledge of the image patterns associated with each subgroup is important in order to predict the molecular characteristics. Objectives Describe, in an hospital population, the imaging characteristics of breast invasive carcinomas according to the four molecular subtypes. Materials and method A descriptive study of 167 patients with invasive breast cancers was performed (81 cases of la, 45 of lb, 24 of tn and 17 of her2) diagnosed at the Department of Mammary Pathology of the Provincial Hospital of the Centenary that had the pathology report, immunohistochemical profile, mammography and breast ultrasound. Results The irregular shape of the mass in mammography was the most frequent in all subtypes, except in tn where the oval form was more prevalent (p<0.0001). The spiculated margin was more frequent in the la (57.4%) and lb (47%); in the tn the obscured margin was more frequent (50%) and in the her2 the margin indistinct (41.6%) (p=0.004). The presence of hyperechoic halo in ultrasound was more frequent in the la (72.9%), lb (80.9%) and her2 (71.4%), whereas the abrupt interface was more frequent in the tn (100%) (p<0.0001 ). The irregular shape of the mass on ultrasound was more observed in la (90.5%), lb (97.6%) and her2 (100%), whereas in the tn was the oval form (60.8%) (p<0.0001). The most frequent orientation of the nodule was not parallel for la (89.1%), lb (100%) and her2 (92.8%), and parallel orientation for tn (65.2%) (p<0.0001). The presence of vascularization was more frequent in la (85.7%), lb (86.2%) and her2 (100%), being less frequent in tn (20%) (p<0.0001). Conclusions la and lb cancers have similar mammographic and ultrasound characteristics. her2 tumors share many of these characteristics, with the exception of margins on mammography. On the other hand, tn tumors present mammographic and ultrasound characteristics different from the other molecular subtypes, simulating benign lesions

Value of MRI in prediction of glioma isocitrate dehydrogenase 1 mutation status / 中国医学影像技术

Objective: To observe the value of MR in prediction of glioma isocitrate dehydrogenase (IDH) 1 mutation status. Methods: Nineteen-two patients with glioma were divided into IDH mutation positive group and negative group, and their imaging characteristics were retrospectively reviewed, including lesions' site, signal intensity, boundary, growth pattern, degree of enhancement and surrounding edema. Then two-class Logistic model was established. Results: There were significant differences between different grades and location of gliomas between the two groups (both P<0.05). There were no significant differences in tumor signal intensity, boundary and growth pattern (P=0.269, 0.606, 0.139). There were statistically significant difference in degree of enhancement and surrounding edema (all P<0.01). Logistic regression analysis showed that the signal uniformity (X1), boundary (X2) and degree of enhancement (X3) of gliomas were statistically significant (P=0.004, 0.037, 0.001), and the regression equation was: logit (P)=2.668+1.415X1-2.097X2-3.229X3 (χ2=41.583, P<0.001), the sensitivity of the model was 70.70%, and the specificity was 80.40%. Conclusion: MRI can be used to non-invasively predict IDH1 mutation status of gliomas before surgical operation.

Expression and significance of SCIN in breast cancer tissue / 中华内分泌外科杂志

Objective To investigate the expression of Scinderin(SCIN myoprotein) in breast cancer tissues and adjacent tissues,and to explore the relationship between the expression of Scinderin and different molecular subtypes of breast cancer as well as the clinical factors.Methods Immunohistochemical staining method was used to detect the expression of SCIN in 120 cases of breast carcinoma and 30 adjacent tissues.The relation between SCIN expression in breast cancer tissue and molecular subtypes,pathologic stage,age,tumor size,lymph node metastasis was analyzed.Results SCIN expression level in breast cancer tissue was lower than in the tissues adjacent to carcinoma (6.06±3.32 vs 7.77±3.32,P＜0.05).SCIN expression was associated with breast cancer molecular subtypes (P＜0.05),and it was irrelevant with age,tumor size,histological grade,lymph node metastasis,or clinical stage (P＞0.05).Conclusions The expression of SCIN in breast cancer tissues was lower than in the adjacent tissues.It is associated with breast cancer molecular subtypes.SCIN could become the protein markers of breast cancer molecular targeted therapy.

Current research status and progress in molecular subtyping of pancreatic cancer / 中华消化外科杂志

Rational molecular subtyping of pancreatic cancer based on genome,transcriptome,proteomics and metabolomics data,in combination with systematic biological analysis,have greatly enriched the traditional histopathological typing methods based on morphology.The introduction of molecular subtyping reflects the progress in deep understanding of the essence of tumorigenesis of pancreatic cancer,providing a necessary foundation for the development of molecular targeted therapy and implementation of precision medicine.Therefore,molecular subtyping of pancreatic cancer has broad application prospects.The current article reviews the current research status and recent progress of molecular subtyping of pancreatic cancer,and discusses the clinical significance of different subtyping methods.

Distribution of molecular subtypes of advanced lung adenocarcinoma and clinical outcomes in a center of Argentina

The prevalence of relevant oncogenic drivers in lung adenocarcinoma varies in our region and data on clinical outcomes is scarce. The objective of the study was to describe the prevalence of KRAS, BRAF and EGFR mutations and ALK translocations in patients with advanced lung adenocarcinoma, and to depict the clinical outcome according to treatment strategies. Patients with adequate tumor biopsy sampling were included. KRAS, BRAF and EGFR mutations were studied by Sanger sequencing. ALK translocations were studied by fluorescent in situ hybridization (FISH) and immunohistochemistry (IH) with antibodies against ALK with clones D5F3 and 5A4. Informed consent was signed by 118 patients and 84 (72%) with complete molecular analysis were included. KRAS mutations were detected in 16 samples (19%), EGFR in 11 (13%), 9 of them conferring sensitivity to EGFR inhibitors, and BRAF mutations in 1 (1%). ALK translocations were detected in 3 samples (4%). Median follow-up was 42.4 [interquartile range (IQR): 27.0-64.2] months. Globally, median overall survival was 10.3 [IQR: 5.6-20.2] months. Median survival was 10.8 [IQR: 6.0-20.3] months in the group of patients without detectable molecular alteration, 9.6 [IQR: 3.7-16.1] months in KRAS mutant population (HR: 1.08; p = 0.82) and 32.5 [IQR: 19.6-38.4] months in patients with ALK translocations or sensitizing EGFR mutated tumors treated with tyrosine kinase inhibitors (HR: 0.27; p = 0.03). In conclusion, the prevalence of molecular alterations and outcomes in our population is similar to that reported in other studies in Western countries.

La prevalencia de alteraciones en oncogenes en adenocarcinoma de pulmón varía en nuestra región. El objetivo fue describir la prevalencia de mutaciones en KRAS, BRAF y EGFR y las translocaciones de ALK en pacientes con adenocarcinoma de pulmón y estudiar la supervivencia de acuerdo a subtipos moleculares. Se incluyeron pacientes con biopsias adecuadas para el estudio. Se evaluó el estado mutacional de KRAS, BRAF y EGFR por secuenciación con la técnica de Sanger. Las translocaciones de ALK se estudiaron por hibridación in situ por fluorescencia (FISH) e inmunohistoquimica (IHQ) contra ALK (clones D5F3 y 5A4). De 118 pacientes evaluados, se incluyeron 84 (72%) con análisis molecular completo. Se detectaron mutaciones de KRAS en 16 muestras (19%), EGFR en 11 (13%), y BRAF en 1 muestra (1%). Se detectaron rearreglos de ALK en 3 muestras (4%). La mediana de seguimiento de los pacientes fue de 42.4 [rango intercuatilo (RIC): 27.0-64.2] meses. Globalmente, la mediana de supervivencia en la población fue 10.3 [RIC: 5.6-20.2] meses y fue de 10.8 [RIC: 6.0 20.3] meses en pacientes sin alteraciones moleculares detectables. La mediana de supervivencia de los pacientes con mutación en KRAS fue de 9.6 [RIC: 3.7-16.1] meses (HR: 1.08; p = 0.82) y 32.5 [RIC: 19.6-38.4] meses en el grupo con rearreglos de ALK o mutaciones en EGFR tratados con inhibidores de tirosina quinasa (HR: 0.27; p = 0.03). En conclusión, la prevalencia de alteraciones moleculares en nuestra población fue similar a otros países occidentales.

Comparison of core needle biopsy and surgical specimens for accurate evaluation of hormonal receptors status and molecular subtypes of breast cancer / 中国肿瘤临床

Objective:To explore concordance between preoperative core needle biopsy(CNB)and resection specimen(RS)in evaluat-ing biomarkers and molecular subtypes with immunohistochemical method.Methods:A retrospective study was performed on 324 breast cancer patients who underwent modified radical mastectomy at the Tianjin Medical University Cancer Institute and Hospital be-tween August 2015 and November 2016.All patients who had received neoadjuvant systemic therapy were excluded.The aim of this analysis was to report concordance between CNB and surgical specimens in evaluating biomarkers,such as ER,PR HER-2,Ki-67,and molecular subtypes.Results:There was concordance between estrogen receptor(ER)assessment on CNB and RS in 94.1%(305/324) of the patients(κ=0.84).Concordance of the progesterone receptor(PR)and the human epidermal growth factor receptor 2(HER-2) assessments were observed in 90.7%(294/324,κ=0.76)and 61.1%(198/324,κ=0.38)patients,respectively.Evaluation of Ki-67 re-vealed an accordance rate of 86.7%(281/324,κ=0.34),and the concordance for immunohistochemistry detection for assessing breast cancer(BC)molecular subtypes was 73.4%(91/124,κ=0.64).Conclusions:Although CNB showed good accuracy for evaluating hormon-al receptor status and BC molecular subtypes,its evaluation of HER-2 and Ki-67 statuses was less accurate than other biomarkers. Therefore,we should combine immunohistochemical results with both CNB and RS samples in order to improve accuracy when diag-nosing molecular subtypes.Moreover,improved diagnoses can provide the basis for more effective systemic therapies.

Relationship between mammographic features and molecular subtypes in invasive breast cancer patients / 中国肿瘤临床

Objective: To assess the relationship between mammographic features and molecular subtypes in invasive breast cancer pa-tients. Methods: We performed a retrospective review of mammographic images from a total of 182 histopathologically diagnosed-breast cancer patients treated in Tianjin Medical University General Hospital and Tianjin Medical University Cancer Institute and Hospi-tal between January 2016 and March 2016. Mammographic features were assessed according to the Breast Imaging Reporting and Da-ta System(BI-RADS). Molecular subtypes were classified according to the St Gallen International Expert Consensus. Statistical analysis was performed to assess the correlation between mammographic features and molecular subtypes of breast cancer. Results: There was a relationship between mammographic calcifications and molecular subtypes of invasive breast cancer (V=0.221, P<0.05). In com-parison with Luminal A (12/20), Luminal B (80/132), and HER-2 enriched (4/10) breast cancers, most triple-negative breast cancers (18/20) were non-calcified lesions (P<0.05). The proportion of spiculated masses was higher in Luminal breast cancer (30/85) than in non-Luminal breast cancer (1/16) (P<0.05). Conclusions: There is a relationship between mammographic features and molecular subtypes of invasive breast cancer.

Correlation of radiomic features based on diffusion weighted imaging and dynamic contrast-enhancement MRI with molecular subtypes of breast cancer / 中华放射学杂志

Objective To explore the relationship between radiomics signatures based on DWI and dynamic contrast-enhanced MRI (DCE-MRI) and molecular subtypes of breast cancer.Methods A retrospective analysis of 79 female breast cancer patients, with single mass, clear molecular subtypes and preoperative breast MRI scanning (obtaining DCE-MRI and ADC images), of Guangdong General Hospital from June 2015 to June 2016,were performed.Traditional quantitative parameters,including ADC value and initial enhancement rate(IER),were recorded.Texture analysis were performed on ADC map and DCE map, with manual segmentation and extraction of radiomic features,and Manual segmentation was performed on ADC map and DCE map, radiomics features were extracted and 10 radiomics signatures were finally selected after dimension reduction. Four molecular subtypes of breast cancer were classified by immunohistochemical detection of pathological specimens, including Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple negative (TN). Univariate logistic regression analysis was used for assessing the performance of ADC values, IER values and radiomics signatures to independently predict molecular subtypes groups.Multivariate logistic regression analysis was performed to establish predicting models, then receiver operating characteristic curves (ROC) were drawn and areas under ROC curve were calculated to compare the diagnostic performance of each model. The Hosmer-Lemeshow test was performed to test the goodness of model fitness. Results There were 29 cases of Luminal A, 39 cases of Luminal B, 5 cases of HER2 overexpression and 6 cases of TN breast cancer patients.Univariate logistic regression analysis was used to assess the ability of traditonal MRI parameters of ADC and IER values and ten of the radiomics siganitures in classifying molecular subtypes,results showed that the AUC values of ADC and IER values, were both less than 0.70 (range 0.516 to 0.605), which indicated valueless;at least one radiomic signature had AUC greater than 0.70 when identifying each molecular subtype, and AUC of DCE_L_G_2.5_autocorrelation achieved the highest value of 0.941 in identifying TN and non-TN subtypes.Multivariate logistic regression analysis were performed to obtain the best model, results showed that the AUCs for classifying Luminal A and non-Luminal A, Luminal B and non-Luminal B, TN and non-TN subtypes were 0.786 and 0.733 And 0.941, respectively. The Hosmer-Lemeshow test showed that the P values of all models were larger than 0.10 (0.156, 0.204 and 0.820,respectively),indicating that there was no significant difference between the predicted and observed values of each model established, these models were all fitted good. Conclusion The radiomics features based on ADC map and DCE map can help to identify the molecular subtypes of breast cancer,especially for the identification of TN type breast cancer.

Triple-negative and non-triple-negative breast cancer prediction by mammographic radiomics features / 中华放射学杂志

Objective To develop and validate a radiomics predictive model based on mammogram for preoperative predicting triple-negative breast cancer (TNBC) or non-triple-negative breast cancer (NTNBC). Methods We retrospectively analyzed 459 Chinese women who were diagnosed with invasive breast cancer (confirmed by pathology) during August 2015 to November 2015. Our cohort included 34 TNBC and random selected 102 NTNBC cases. Regions of interest (ROIs) were manually selected from craniocaudal and mediolateral oblique mammograms by radiologists through manual lesion segmentation, and 43 radiomics features were evaluated. Craniocaudal (CC) single-view, mediolateral oblique (MLO) single-view and CC and MLO double-view classification model were constructed respectively. Classification performance was evaluated by the area under receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. Kruskal-Walls U test and t test were used to compare the radiomics features between TNBC and UTNBC. Results The model that used the combination of both the CC and MLO view images achieved the overall best performance than using either of the two views alone, yielding an AUC of 0.791, accuracy of 0.798, sensitivity of 0.776 and specificity of 0.806 for TNBC comparing with NTNBC. Three features were selected by the model (gray scale span and inverse different moment for CC, roundness for MLO) showed a statistical significance (P<0.05) and AUC>0.6 in the subtype classification. Conclusion This research constructed model based on mammograms classification model can effectively distinguish between TNBC and NTNBC. This model has potential value for breast cancer molecular subtype classification and clinical treatment.