乳腺癌新辅助化疗疗效与分子分型的关系

目的探讨乳腺癌分子分型与表柔比星联合多西他赛（TE）方案新辅助化疗疗效的关系。方法根据纳入和排除标准,共纳入我院2011年5月至2012年12月期间至少接受过3周期TE方案治疗的乳腺癌患者共239例,其各项临床指标均完整。根据免疫组织化学雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及Ki-67表达水平将患者分为4种亚型,分别为luminal A型、luminalB型、HER-2阳性型和三阴型。分析不同亚型乳腺癌患者的各项相关指标,如病理完全缓解（pCR）率、年龄、月经状态等。结果239例患者中,luminalA型67例（28．03％）,luminalB型84例（35．15％）,HER．2阳性型21例（8．79％）,三阴型67例（28．03％）。4型乳腺癌患者的年龄、月经状态、肿瘤大小、淋巴结状态等临床病理指标差异均无统计学意义（P〉0．05）。三阴型对TE方案的新辅助化疗的pCR率（14．93％）最高,其次依次为luminalB型（7．14％）、HER-2阳性型（4．76％）及luminalA型（1．49％）,差异有统计学意义（P=0．027）。结论三阴型相对luminalA型、luminalB型和HER-2阳性型对TE方案的新辅助化疗治疗更敏感,pCR率最高,治疗时需根据患者不同的分子亚型来选用特定的治疗方案。     

Intratumoral Heterogeneity of Genetic Changes in Primary Colorectal Carcinomas with Metastasis

Purpose. To elucidate the intratumoral distribution of genetic changes, surgically resected colorectal carcinomas were investigated regarding their loss of heterozygosity in the regions of tumor suppressor genes and the mutation of ras genes. Methods. Full-thickness fresh tumor slices from 23 colorectal carcinomas were removed and divided into multiple specimens, which were then submitted separately for DNA and histopathological analyses. The loss of heterozygosity was analyzed in 23 primary carcinomas and 9 metastasized carcinomas by the use of restriction fragment-length polymorphism markers on chromosome 1p, 5q, 17p, 18q, and 22q. Results. Intratumoral heterogeneity was identified in 11 of 23 primary carcinomas (47.8%) and we could successfully map the regional genetic variation. In both stages I and II, 1 of 5 cases (20%); in stage III, 3 of 6 cases (50%); and in stage IV, 6 of 7 cases (85.7%) were heterogeneous. With respect to venous invasion positive primary carcinomas, hepatic metastasis occurred in 75% (6/8) of the heterogeneous carcinomas, whereas hepatic metastasis occurred in only 12.5% (1/8) of homogeneous carcinomas. Conclusion. The present results suggest that the existence of intratumoral heterogeneity, which may reflect genetic instability, may thus play a role in the enhancement of aggressive progression and the metastasis of colorectal carcimomas. Received: June 11, 2002 / Accepted: November 19, 2002 RID="*" ID="*" Reprint requests to: M. Miyaki     

CyclinD1在不同分子亚型乳腺癌中的表达及其对预后的影响

目的检测cyclinD1在不同分子亚型乳腺癌中的表达,分析其表达与临床病理特征和预后的关系。方法采用免疫组织化学法检测175例乳腺癌组织标本中cyclinD1的表达情况,应用卡方检验分析cyclinD1在不同分子亚型乳腺癌中的表达,采用Spearman秩相关方法分析cyclinD1表达与临床病理特征的相关性,运用Kaplan．Meier生存曲线分析cyclinD1不同表达对预后的影响。结果①CyclinD1阳性表达在LuminalA型所占比例最高（P〈0．05）,而cyclinDI阴性表达在LuminalB型所占比例最高（P〈0．05）。②CyclinD1阳性表达与临床分期、组织学分级及PR无关（P〉0．05）,与淋巴结转移数目（rs=0．197,P〈0．01）、ER呈正相关（rs=0．139,P〈0．05）;cyclinD1阳性表达与Her-2呈负相关（rs=0．131,P〈0．05）。③CyclinD1阳性表达越强,无瘤生存时间越长（P〈0．05）。结论CyclinD1阳性表达与ER、Her-2及淋巴结转移数目有明显相关性,且其阳性表达提示相对良好的预后,可作为乳腺癌预后评估的参考指标。     

Morphologic and Molecular Characteristics of Bladder Cancer

Bladder cancer is the fourth most common cancer in men, and is associated with significant morbidity and mortality. Pathologic evaluation of urothelial cancers relies predominantly on histomorphologic features but can be aided in a small subset of cases by immunohistochemical analyses. Distinction of papillary versus flat lesions, low-grade versus high-grade cytology, and histologic variants and the presence or absence of invasive tumor is important for proper clinical management. Advances in the molecular alterations associated with the various subtypes of urothelial carcinoma have been made but such studies are ongoing.     

Invasive Breast Cancer: Recognition of Molecular Subtypes

SUMMARY: Molecular profiling has fundamentally changed our understanding of breast cancer in the last 10 years, by creating a new taxonomy of breast cancers based on the expression patterns of so-called 'intrinsic genes'. Hierarchical clustering analyses performed on microarray-based gene expression profiles of breast cancers defined distinct breast cancer subgroups (luminal type A/B, HER2-enriched type, basal-like type). Since the initial landmark study by Perou et al., the concept of intrinsic breast cancer subtypes has been corroborated and expanded by several independent research groups. Further studies revealed individual properties of the intrinsic subgroups regarding the clinical course and the responsiveness to chemotherapy. The new gene expression profile-based taxonomy of breast cancer has been enthusiastically embraced by the scientific community and hailed as a major breakthrough on the way to individually tailored therapies. However, validation of the gene signatures in prospective studies is necessary before accepting these new technologies in daily clinical practice. In this review, the current data regarding the intrinsic subtypes and the associated clinical implications as well as the methodology of molecular profiling and possible use of immunohistochemistry in identifying intrinsic subtypes are discussed.     

Molecular Breast Cancer Subtypes in Premenopausal African-American Women,Tumor Biologic Factors and Clinical Outcome

Introduction Breast cancer is currently viewed as a heterogeneous disease made up of various subtypes, with distinct differences in prognosis. Our goal was to study the distribution and to characterize the clinical and biological factors that influence the behavior and clinical management of the different molecular breast cancer subtypes in premenopausal African-American women. Methods A retrospective analysis of Howard University Hospital tumor registry, for all premenopausal African-American women aged less than 50 years, diagnosed with breast cancer from 1998–2005, was performed. Results The luminal A subtype was the most prevalent (50.0%), vs basal-cell-like (23.2%), luminal B (14.1%), and HER-2/neu (12.7%). However when stratified by age groups, results showed that in the age group <35 years the basal-cell-like subtype was the most prevalent (55.6%), vs 25.9%, 14.8%, and 5.6% for luminal A, luminal B, and HER-2/neu subtypes, respectively (P < .000). P53 mutation was more prevalent in the basal-cell-like subtype compared to luminal A (48.0% vs 18.6%, P < .01). The expression of the Bcl-2 gene differed by subtype, with the luminal A and luminal B subtypes more likely to overexpress the Bcl-2 gene (89.1% luminal A, 80.0% luminal B vs 47.6% basal-cell-like and 40.0% HER-2/neu, P < .000). Though not statistically significant, HER-2/neu and basal-cell-like subtypes had the shortest survival time (P < .31). Conclusion The high prevalence of the basal-cell-like subtype in young premenopausal African-American women aged <35 years may contribute to the poorer prognosis observed in this cohort of African-American women.     

Marked Intratumoral Heterogeneity of the Proto-Oncogene Her-2/neu Determined by Three Different Detection Systems

Abstract: It is customary to submit only one portion of a breast cancer to determine if there is amplification or overexpression of the proto-oncogene HER-2/ neu. In routine studies of the expression of neu in breast cancer, however, we noted discrepancies in intratumoral positivity. To investigate this phenomenon further, multiple tumor specimens (129 samples) from 41 women with breast cancer were examined. Forty cases were analyzed for neu amplification by slot blot assay and 18 with fluorescent in situ hybridization. Neu overexpression was determined using four different specific antibodies. In more than 50% of cases there were discrepancies in results between the tissue blocks examined. This was evident in both inter- and intra-assay comparisons. It is concluded that intratumoral heterogeneity of neu amplification/overexpression in breast cancer exists to a far greater degree than previously recognized and could be a responsible factor for conflicting published data regarding neu 's prognostic significance. Examination of only one tumor sample may not give a true indication of either amplification or overexpression of this oncogene.     

DLL4和S100A4在不同分子亚型乳腺癌组织中的表达及意义

目的 分析Delta样配体4(Delta-like ligand 4,DLL4)及S100钙结合蛋白A4 (S100 calcium binding protein A4,S100A4)在不同乳腺癌分子亚型组织中的表达并讨论其临床意义.方法 采用免疫组织化学SP法检测十堰市太和医院Luminal A型乳腺癌组织51例、Luminal B型乳腺癌组织26例、HER-2过表达型乳腺癌组织17例、基底细胞样型乳腺癌组织14例和乳腺癌癌旁组织40例中DLL4和S100A4的表达情况,并分析其与乳腺癌临床病理特征之间的关系.结果 在乳腺癌组织中,DLL4和S100A4的表达阳性率分别为67.6％ (73/108)和62.0％ (67/108),均高于其在癌旁组织中的表达阳性率[22.5％ (9/40),45.0％ (18/40)],P＜0.05.在不同乳腺癌分子亚型组织中,HER-2过表达型和基底细胞样型乳腺癌组织中DLL4和S100A4的表达阳性率均高于LuminalA型和LuminalB型(P＜0.05).有淋巴结转移的乳腺癌患者,DLL4和S100A4呈高表达(P＜0.05).乳腺癌组织中DLL4表达与S100A4表达呈正相关关系(rs=0.217,P＜0.01).结论 DLL4和S100A4在基底细胞样型和HER-2过表达型乳腺癌组织中呈高表达,与预后相关.DLL4和S100A4共同参与乳腺癌的发生、发展以及浸润转移过程.临床联合检测两种蛋白表达可评估乳腺癌的潜在转移和预后.     

Urothelial Bladder Cancer: An Update on Molecular Pathology with Clinical Implications

Urothelial bladder cancer is a heterogenous disease with distinct clinical and histopathological features. In the last few years it became clear that papillary, mostly noninvasive, disease with few molecular changes and aggressive urothelial carcinoma are genomically separate diseases. Recently, several studies found that invasive bladder cancer can also be separated into several molecular subgroups. In the present review we summarize molecular alterations, diagnostic markers, and molecular subgroups in urothelial bladder cancer and discuss their clinical relevance for prognosis, prediction of recurrence and progression, and therapeutic response to chemotherapy, radiotherapy, and immunotherapy.     

Variants of Bladder Cancer: The Pathologist's Point of View

Pathologic evaluation of bladder cancer typically reveals great tumor heterogeneity and, therefore, the common observation of urothelial carcinoma exhibiting a wide variety of histopathologic patterns is not surprising. Some of these patterns are so distinctive that they have been recognized as specific variants of urothelial carcinoma. Classifications have recently been revised in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The current World Health Organization classifications clarify terminological issues and provide better definition criteria, but also incorporates some new entities. Many of these variants have important prognostic or therapeutic implications worth knowing by the urologist and oncologist, but also represent diagnostic challenges in daily practice of pathology. This review will discuss the features of pathologic variants of bladder cancer in the context of our current clinical practice.     

Molecular subtyping reveals uniqueness of prognosis in breast ductal carcinoma in situ patients with lumpectomy

BackgroundWe aimed to analyse the discrepancy in clinical features and prognosis between molecular subtypes in primary ductal carcinoma in situ (DCIS) patients with lumpectomy.MethodsPrimary DCIS patients were identified from the Surveillance, Epidemiology, and End Results registries database from 2010 to 2017. Based on immunohistochemistry markers of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), enrolled DCIS cases were divided into four molecular subtypes, HR-HER2-, HR-HER2+, HR + HER2+, and HR + HER2-. Clinical features and prognosis were compared between molecular subtypes. Radiotherapy (RT) effects on prognosis were also analysed in each molecular subtype.ResultsA total of 5,628 DCIS cases were retrospectively enrolled in this study. HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- are 299 (5.3%), 498 (8.8%), 1,086 (19.3%), and 3,745 (66.5%), respectively. HR + HER2- cases have smaller tumor size (72.6%, P < 0.001) and lower grade (23.5%, P < 0.001). Comedo necrosis is more frequent in HR-HER2- (24.4%, P < 0.001) and HR-HER2+ DCIS cases (24.3%, P < 0.001). In univariate analyses, HR-HER2+ cases have significantly higher ipsilateral breast event (IBE) recurrence than HR+HER2- cases (P = 0.010). HR-HER2- cases show higher disease-specific mortality than HR+HER2+ cases (P = 0.021). In high-risk DCIS cases, RT reduces the absolute 5-year IBE incidence by 1.3%, 0.7%, 1.9%, and 2.6%, respectively in HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- cases, respectively.ConclusionIn this population-based study, DCIS cases have diverse clinical and prognostic features for different molecular subtypes. Adjusting treatment strategies according to DCIS molecular subtypes is worth advancing.     

Molecular Genetics of Pancreatic Neoplasms

Pancreatic neoplasms have a wide range of histologic types with distinct clinical outcomes. Recent advances in high-throughput sequencing technologies have greatly deepened our understanding of pancreatic neoplasms. Now, the exomes of major histologic types of pancreatic neoplasms have been sequenced, and their genetic landscapes have been revealed. This article reviews the molecular changes underlying pancreatic neoplasms, with a special focus on the genetic changes that characterize the histologic types of pancreatic neoplasms. Emphasis is also made on the molecular features of key genes that have the potential for therapeutic targets.     

Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting

Context

Although a number of studies have demonstrated the importance of constitutively active androgen receptor variants (AR-Vs) in prostate cancer, questions still remain about the precise role of AR-Vs in the progression of castration-resistant prostate cancer (CRPC).