Tumour DNA ploidy as an independent prognostic factor in breast cancer

We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P less than 0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer, primarily in cases with steroid receptor-positive tumours. In a Cox multivariate analysis DNA ploidy (P = 0.001), primary tumour size (P = 0.0007), nodal status (P = 0.04) and the content of progesterone receptors (P = 0.0008) emerged as significant independent prognostic factors, whereas oestrogen receptor status, age and menopausal status of the patients had no significant independent prognostic value. If the histological grade of ductal carcinomas was also included in the Cox model, both grade and DNA ploidy had independent prognostic effect. In conclusion, our results indicate that the analysis of DNA ploidy is a useful adjunct in the assessment of prognosis for breast cancer patients.     

DNA analysis of cholangiocarcinoma cells: prognostic and clinical importance

INTRODUCTION: The clinical value of established prognostic factors seems to be limited since they fail to predict reliably survival of patients after resection of cholangiocarcinoma. DNA ploidy reflecting irregularities of chromosome number and content might be an alternative predictor. In this study, we evaluated the DNA ploidy as a prognostic factor for survival of patients after resection of cholangiocarcinoma. METHODS: This prospective study included 34 patients with cholangiocarcinoma which were surgically resected and followed up to death or more than 3 years. Tissue specimens were taken from the liver tissue immediately after resection and DNA ploidy determined. Survival was related to the type of DNA ploidy as well as to five established prognostic factors. RESULTS: Multivariate analysis revealed that in this study only DNA ploidy (P = 0.012) was significantly associated with prediction of survival. In contrast, neither tumor stage pT (P = 0.073) nor tumor grade pG (P = 0.154), resection margins R (P = 0.322), metastasis M (P = 0.060), lymph node stage pN (P = 0.209), age (P = 0.13) nor sex (P = 0.849) could significantly predict survival. Three-year survival was best for patients with diploid tumors (n = 6) of whom 75% survived more than 3 years. Poor prognostic signs associated with short term survival of less than 18 months were tumors classified as aneuploid (n = 17), large tumors pT4 (n = 8), metastasis pM1 (n = 11), undifferentiated tumors pG3 (n = 9) and non-tumor-free resection margins R2 (n = 14). The best predictor for poor prognosis was aneuploidy since it could identify more patients with a fatal outcome than other prognostic factors. DNA ploidy turned out to discriminate highly significant between diploid, polyploid and aneuploid tumors. DISCUSSION: The most accurate prognostic factor for survival of patients after resection of cholangiocarcinoma was DNA ploidy. Most patients suffering from a diploid tumor turned out to be long term survivors whereas aneuploid tumors indicated a poor prognosis with a rather short survival time of less than 18 months. We conclude that DNA ploidy is a valuable diagnostic tool for identifying subgroups of patients that are at higher risk for tumor progression.     

Comparison between screen-detected and symptomatic breast cancers according to molecular subtypes

Breast cancer screening programs make it possible to detect early cancer, thus reducing breast cancer mortality. We studied the clinicopathologic characteristics and prognosis of screen-detected invasive breast cancer compared with symptomatic breast cancer. And we compared the result according to molecular subtypes (luminal A, luminal B, Her2, and triple negative), with the goal of identifying the role of screening in each subtypes. From January 2002 to June 2008, 3,141 patients who underwent surgery for the treatment of invasive ductal carcinoma at Samsung Medical Center were included. Among them, 1,025 patients were screen-detected, and 2,116 patients who were screened over 2 years or never were symptomatic. We retrospectively reviewed the clinical and pathologic data. Screen-detected breast cancer was associated with older age, smaller tumor size, more hormone-receptor positive, less lymph node involvement, earlier stage, and reduced mortality compared with symptomatic breast cancer (P < 0.001). According to the molecular subtype, luminal A was most common (63.6%) and showed the most obvious survival benefit in screen-detected tumors in comparison with symptomatic tumors (5-year OS: 99.7 vs. 96.5%, 5-year DFS: 96.4 vs. 90.7%). Screen detection was independently associated with improved overall and disease-free survival outcomes after adjustment for covariates (HR 0.32, P = 0.035; HR 0.58, P = 0.020, respectively) only in the luminal A subtype. Differences in pathological features such as tumor size, nodal status, grade, and age at diagnosis with different molecular subtype distributions may explain the survival advantage of patients with screen-detected breast cancer. Screening programs seem to have a different efficacy depending on the molecular subtype of the breast cancer, especially in the luminal A subtype, for which screen detection acts as an independent prognostic factor itself.     

Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma

BACKGROUND: Several studies have shown the prognostic value of desmoplasia for lung adenocarcinomas. The authors evaluated the density and extent of desmoplasia by modifying the scar grade, as well as the prognostic impact on patient survival. METHODS: Modified scar grade was defined as follows: Grade 1, no desmoplasia; Grade 2, sparse desmoplastic reaction; Grade 3, dense desmoplastic reaction with diameter of 10 mm or less; Grade 4, dense desmoplastic reaction with diameter exceeding 10 mm. In addition, the prognostic impact of conventional histologic factors and modified scar grade was analyzed in 239 cases of small peripheral lung adenocarcinoma (maximum dimension, 相似文献   

Prognostic significance of flow cytometric DNA analysis in node-negative breast cancer patients

Flow cytometric DNA analysis using paraffin-embedded tumor blocks was done retrospectively on 155 node-negative breast cancers. The median duration of follow-up in patients still alive at the time of analysis was 10 years. Tumor aneuploidy was correlated significantly with increased tumor size (P = 0.003) and higher tumor grade (P less than 0.001). No significant correlation between tumor ploidy and patient age was found. Patients with diploid tumors had a significantly improved relapse-free and overall survival compared with patients with aneuploid tumors (P = 0.0001). In a Cox multivariate model with parameters including ploidy, histologic grade, tumor size, and patient age, ploidy (P = 0.02) and tumor size (P = 0.05) emerged as significant independent predictors of overall survival. Only ploidy was independently significant in the analysis of relapse-free survival. In conclusion, the current study indicates that flow cytometric measurement of DNA ploidy is a powerful prognostic indicator in node-negative breast cancer patients.     

Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma

BACKGROUND: Papillary thyroid carcinomas represent a diversity of morphologic subtypes and variants, but to the authors' knowledge the prognostic significance of subclassification is not clear. Therefore, the authors compared the value of histologic classification with a combined assessment of histologic key features such as marked nuclear atypia, tumor necrosis, and vascular invasion (i.e., histologic grade). METHODS: One hundred twenty-eight surgically treated patients with papillary carcinoma > 10 mm were studied. The tumors were subclassified and individual histologic features were examined and compared in univariate and multivariate survival analyses. RESULTS: Of all the cases, 55% were of the usual type, whereas 27% showed complex histologic features with different components present and 18% represented specific subtypes. Tall cell differentiation showed an increased frequency of tumor necrosis and vascular invasion, and tumors with solid areas had an increased occurrence of mitotic figures and vascular invasion. Patients with tall cell tumors tended to have reduced survival (P = 0.074), and two patients with columnar cell features died of the disease. When combined, the group of patients with all tumor subtypes had significantly reduced survival when compared with the remainder of patients (P = 0.034), although the difference was only minor. Histologic grade was highly significant (P = 0.0001) in survival analysis, together with mitotic frequency (P = 0.028), S-phase (P = 0.015), and G(2)M-phase fractions (P = 0.040). In multivariate analysis, tumor dimension (P = 0.019) and histologic grade (P = 0. 008) showed significant and independent prognostic importance, whereas subclassification was not found to be significant. CONCLUSIONS: Subclassification of papillary thyroid carcinomas had only a minor prognostic impact, whereas histologic grade was a strong and independent prognostic marker. The authors recommend that all papillary carcinomas be given a histologic grade based on a combined examination of nuclear atypia, tumor necrosis, and vascular invasion. [See editorial on pages 1766-68, this issue.] Copyright 2000 American Cancer Society.     

The prognostic significance of tumor ploidy and pathology in adenocarcinoma of the esophagogastric junction

Tumor DNA content has been advocated to be an important prognostic indicator in human malignancies. Paraffin-embedded specimens of 75 resected adenocarcinomas (AC) of the esophagogastric junction were studied by flow cytometric DNA analysis to determine whether tumor ploidy was a significant prognostic variable independent of stage and histologic grade of the tumor. Eighty-one percent of the tumors were aneuploid. More patients with aneuploid tumors had lymph node metastases than patients with diploid tumors (P = 0.007). Patients with aneuploid tumors had poorer 18-month disease-free and overall survival than patients with diploid tumors. Cox regression analysis demonstrated that the most important prognostic variables for predicting overall survival were lymph node status, depth of wall invasion, and tumor differentiation. Tumor ploidy was not an independent prognostic variable in predicting recurrent disease or death from AC of the esophagogastric junction. Tumor DNA content is valuable, however, as a marker for patients at increased risk of lymph node metastases, early recurrence, and poorer survival.     

腹膜后脂肪肉瘤亚型转换的相关因素及预后分析

目的:回顾性分析腹膜后脂肪肉瘤（retroperitoneal liposarcoma ,RPLS）亚型转换及预后的影响因素,以指导临床实践。方法:回顾性分析1997年7 月至2014年10月年河南省肿瘤医院收治的经术后病理证实的92例腹膜后脂肪肉瘤患者的临床资料,复习相关文献并对其预后进行随访,对可能影响亚型转换及预后的相关因素进行统计分析。结果:瘤体分叶（P = 0.013）能促进亚型转换;符合入组条件的74例腹膜后脂肪肉瘤患者,总5 年生存率48.65% ,Log-rank 检验首诊年龄> 45岁（P = 0.045）、联合脏器切除（P = 0.042）、瘤体坏死（P < 0.001）、亚型转换（P < 0.001）、首发病理亚型的恶性级别（P < 0.001）是影响患者预后的因素。多因素回归分析显示瘤体坏死及首发病理亚型是影响患者预后的独立影响因素。结论:瘤体分叶能促进脂肪肉瘤亚型转换,腹膜后脂肪肉瘤患者预后与首诊年龄、联合脏器切除、瘤体坏死、亚型转换和首发病理亚型有关,联合脏器切除不能改善复发性腹膜后脂肪肉瘤的5 年生存率,放化疗不能改善患者的预后。      

Breast cancer-specific survival by clinical subtype after 7 years follow-up of young and elderly women in a nationwide cohort

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20–89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70–89) more often had luminal A-like tumors. Compared to age 50–59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81–2.82), while elderly had two to five times higher mortality rate (70–79: HR = 2.25, 1.87–2.71; 80–89: HR = 5.19, 4.21–6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.     

Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry

Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy.     

International neuroblastoma pathology classification for prognostic evaluation of patients with peripheral neuroblastic tumors: a report from the Children's Cancer Group.

BACKGROUND: The International Neuroblastoma Pathology Classification was established in 1999 for the prognostic evaluation of patients with neuroblastic tumors (NTs). METHODS: Pathology slides from 746 NTs (the Children's Cancer Group [CCG]-3881 and CCG-3891 studies) were evaluated according to the International Classification. First, prognostic effects of the morphologic indicators (grade of neuroblastic differentiation: undifferentiated [U], poorly differentiated [PD] and differentiating [D]; and mitosis-karyorrhexis index [MKI]: low [L-MKI], intermediate [I-MKI], and high [H-MKI]) for tumors in the neuroblastoma (NB) category were tested. Then, prognostic significance of the International Classification for all NTs in four categories (neuroblastoma [NB]; ganglioneuroblastoma, intermixed [GNBi]; ganglioneuroma [GN]; and ganglioneuroblastoma, nodular [GNBn]) was analyzed. Finally, age distribution of the patients in the four categories as well as three subtypes (based on the grade of differentiation) in the NB category was compared. RESULTS: There were 630 NB tumors, 30 GNBi tumors, 10 GN tumors, and 76 GNBn tumors. In the NB category, prognostic effects of the indicators (three grades of differentiation and three mitosis-karyorrhexis index [MKI] classes: low [L], intermediate [I], and high [H]) were affected significantly by the age of the patients. The age-linked evaluation of the indicators according to the International Classification successfully distinguished two prognostic subgroups: the favorable histology (FH) subgroup (PD/D and L/I-MKI tumors in patients age < 1.5 years, D and L-MKI tumors in patients ages 1.5-5.0 years; 90.4% 5-year event free survival [EFS]) and the unfavorable histology (UH) subgroup (U and/or H-MKI tumors in patients of any age, PD and/or I-MKI tumors in patients ages 1.5-5.0 years, any grade of differentiation, and any MKI class in patients age > or = 5 years; 26.9% EFS) (P < 0.0001). The International Classification also distinguished the FH group (FH subgroup with NB, GNBi, and GN tumors) and the UH group (UH subgroup with NB and GNBn tumors) for all NTs (90.8% EFS and 31.2% EFS, respectively; P < 0.0001) and provided independent prognostic information on both patient age and disease stage (P < 0.0001). Among patients with FH tumors, the median ages of patients with the PD and D subtype tumors in the NB category were 0.43 years (range, 0-1.50 years) and 1.50 years (range, 0.02-4.65 years), respectively, and the median ages of patients with GNBi and GN tumors were 3.51 years (range, 0.96-14.85 years) and 4.80 years (range, 1.94-17.05 years), respectively. In contrast, patients with UH tumors generally were older when they were diagnosed, and with median ages of 2.99 years (range, 1.30-8.84 years) for patients with U subtype tumors, 2.59 years (range, 0.0-12.57 years) for patients with PD subtype tumors, 2.16 years (range, 0.35-9.90) for patients with D subtype tumors, and 3.26 years (range, 0.57-15.90 years) for patients with GNBn tumors. CONCLUSIONS: This study confirmed the prognostic significance of the International Classification, substantiated age-linked prognostic effects of the morphologic indicators for patients with the tumors in the NB category, and supported the concept of an age-appropriate framework of maturation for patients with the tumors in the FH group.     

A retrospective study of breast cancer subtypes: the risk of relapse and the relations with treatments

Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate relapse for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. The study population included primary, operable 2,118 breast cancer patients, all non-specific infiltrative ductal carcinoma, with the median age of 53.2 years. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 were analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpressing, basal-like, and unclassified subtypes. Ki-67 was detected in luminal A subtype. The median follow-up time was 67.9 months. Luminal A tumors had the lowest rate of relapse (12.7%, P < 0.001), while luminal B, HER2 overexpression, and basal-like subtypes were associated with an increased risk of relapse (15.7, 19.1, 20.9%). Molecular subtypes retained independent prognostic significance (P < 0.001). In luminal A subtype, adjunctive radiotherapy could decrease the risk of relapse (P = 0.005), Ki67 positive was a high-risk factor for relapse (P < 0.001), and adjuvant chemotherapies could reduce the relapse for the patients with risk factors (P < 0.001). Adjuvant hormone therapy was an effective treatment for ER-positive tumors (P < 0.001). Molecular subtypes of breast cancer could robustly identify the risk of recurrence and were significant in therapeutic decision making. The model combined subtype and clinical pathology was a significant improvement. Luminal A tumors might represent two distinct subsets which demonstrated distinct prognosis and therapy response.     

乳腺癌分子分型在新辅助化疗疗效和预后中的预测作用

[目的]探讨乳腺癌分子分型在新辅助化疗疗效及预后预测中的作用.[方法]对接受新辅助化疗方案治疗的157例乳腺癌患者进行回顾性分析.依据免疫组化雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(Her2)表达水平将乳腺癌分为Luminal A、Luminal B、Her2阳性和三阴性4个分子分型,分析4个分子分型与临床病理因素、新辅助化疗疗效及3年生存率的相关性.[结果] 157例患者中,分子分型与肿瘤大小、淋巴结转移相关,T3～4期的三阴性型的比例高于T1～2期(P=0.003);N0、N1、N2、N3期的三阴性型的比例分别为44.4％、23.8％、25.6％和22.2％ (P=0.014).不同分子分型间新辅助化疗有效率无明显差异(P=0.632),而T分期(P=0.014)、N分期(P=0.031)与有效率明显相关.不同分子分型间新辅助化疗3年生存率有明显差异,Luminal A型最高,三阴性型最低(P=0.049).乳腺癌预后影响因素Cox回归模型分析提示分子分型(P=0.003)、年龄(P=0.007)、T分期(P=0.013)、N分期(P=0.000)是乳腺癌患者的独立预后因素.[结论]乳腺癌分子分型与肿瘤大小、淋巴结转移状态相关,能作为新辅助化疗远期疗效的独立预测因子.     

Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients.

PURPOSE: Formalin-fixed, paraffin-embedded tissues from axillary node-negative breast cancer patients were analyzed by flow cytometry to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF). PATIENTS AND METHODS: All patients were registered on a good-risk control arm of an intergroup clinical trial. They had small- to intermediate-sized (less than 3 cm), estrogen receptor (ER)-positive tumors and received no adjuvant therapy after modified radical mastectomy or total mastectomy with low axillary-node sampling. The median follow-up was 4.8 years. RESULTS: Assessable ploidy results were obtained from 92% of the 298 specimens studied (51% diploid, 49% aneuploid), and SPFs were assessable for 83% of the tumors. SPFs for diploid tumors ranged from 0.7% to 11.9% (median, 3.6%), compared with a range of 1.2% to 26.7% (median, 7.6%) for aneuploid tumors (P less than .0001). No significant differences in disease-free or overall survival were observed between patients with diploid and aneuploid tumors. Using different SPF cutoffs by ploidy status (4.4% for diploid, 7.0% for aneuploid), patients with low SPFs had significantly longer disease-free survival rates than patients with high SPFs (P = .0008). The actuarial 5-year relapse rates were 15% and 32% for patients with low (n = 142) and high SPFs (n = 105), respectively. Similar relationships between SPF and clinical outcome were observed for patients with diploid tumors (P = .053) and for patients with aneuploid tumors (P = .0012). CONCLUSION: S-phase fraction provides additional prognostic information for predicting disease-free survival for axillary node-negative breast cancer patients with small, ER-positive tumors.     

新疆地区1006例不同分子分型乳腺癌的临床病理特征及预后

目的 探讨新疆地区不同分子分型乳腺癌的临床病理特征和预后。方法 收集2008年1月至2010年12月新疆医科大学附属肿瘤医院行手术治疗的1006例女性乳腺癌患者的临床病历资料,根据雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体-2（HER-2）和Ki-67的状态,将乳腺癌分为：Luminal A型、Luminal B型、HER-2过表达型及Basal like型,对比分析不同分子分型乳腺癌患者的临床病理特征、复发转移及预后情况。结果 Luminal A型551例（54.8％）,Luminal B型182例（18.1％）,HER-2过表达型77例（7.7％）,Basal-like型196例（19.4％）。不同分子分型乳腺癌在肿块大小、淋巴结转移数目、临床分期、组织学分级、民族及内分泌治疗的差异均具有统计学意义（P＜0.05）。获得随访的971例患者中,HER-2过表达型的局部复发率（12.3％）及远处转移率（27.4％）均高于其他分型（P＜0.05）。Luminal A型、Luminal B型、HER-2过表达型及Basal-like型6年无病生存率分别为86.8％、75.8％、58.9％、79.1％（P＜0.05）;6年生存率分别为92.1％、83.1％、67.1％、88.0％（P＜0.05）。Cox多因素回归分析显示,淋巴结转移数目、组织学分级、内分泌治疗及分子分型是影响新疆地区乳腺癌总生存时间（OS）和无病生存时间（DFS）的独立因素,民族亦是影响该地区乳腺癌患者DFS的独立因素。结论 新疆地区Luminal A型乳腺癌最常见,预后最好,HER-2过表达型比例最低,预后最差。乳腺癌预后与淋巴结转移数目、组织学分级、内分泌治疗及分子分型有关,民族是影响乳腺癌患者DFS的重要因素。     

Prognosis of a series of 763 consecutive node-negative invasive breast cancer patients without adjuvant therapy: analysis of clinicopathological prognostic factor.

BACKGROUND AND OBJECTIVES: The objectives of this study were to confirm the favorable outcome of Japanese invasive breast cancer patients without lymph node metastasis, after treatment with surgery alone, and to evaluate clinicopathological prognostic factors in this population. METHODS: The subjects were 763 consecutive node-negative invasive breast cancer patients who underwent surgery without adjuvant therapies between 1988 and 1993 at our hospital. Disease-free survival (DFS) and overall survival (OS) rates were analyzed by clinicopathological factors. RESULTS: The median age of the patients at surgery was 52 years and the median follow-up period of patients was 74 months. At 5 years, the respective DFS and OS rates of all patients were 90.8% and 93.9%. Patients with a pathological tumor size of invasive component of more than 2 cm (319 patients) had a significantly lower DFS than those with tumors measuring 2 cm or less (361 patients) (P = 0.045). Patients with positive hormone receptor status (280 patients) (estrogen and/or progesterone receptor positive) tended to have a better OS than those negative for both hormone receptors (92 patients) (P = 0.078). Meanwhile, patients with tumors of histological grade 3 (328 patients) had a much poorer prognosis than those with tumors of histological grade 1 or 2 (413 patients) (P = 0.008 for OS and P = 0.042 for DFS). The respective 5-year DFS and OS rates of patients with histological grade 3 tumors larger than 2 cm in pathological tumor size of invasive component (195 patients) were 85.5% and 87.6%, indicating that these node-negative patients form a high risk group. CONCLUSIONS: Japanese invasive breast cancer patients without lymph node metastasis tended to show a survival advantage compared with their Caucasian counterparts. Histological grade was the most useful prognostic factor in this population.     

腋窝淋巴结阴性浸润性乳腺癌分子分型的表达及预后分析

  目的   探讨腋窝淋巴结阴性浸润性乳腺癌不同分子分型的分布,临床病理特征以及和预后的关系。   方法   回顾性分析183例该类乳腺癌患者的临床病理资料,对管腔上皮（Luminal）型、基底样（Basal-1ike）型和HER-2过表达（over-expression）型乳腺癌患者在年龄、肿瘤大小、临床分期和无瘤生存率（disease-free survival,DFS）、总生存率（overall survival,OS）方面进行统计分析。   结果   不同分子亚型乳腺癌在年龄、肿瘤大小、临床分期方面无显著性差异。Luminal、Basal-like、HER-2过表达型的复发率分别为3.9%（4/102）、20.4%（10/49）、6.3%（2/32）（P=0.002）;死亡率分别为2.0%（2/102）、6.1%（3/49）、3.1%（1/32）（P>0.05）。Ka-plan-Meier分析显示Basal-like型的DFS最低（P=0.002）,Basal-like型的OS较低（P=0.39）。Cox多因素比例风险模型分析显示分子亚型对DFS存在显著影响（P=0.001）。   结论   在腋窝淋巴结阴性浸润性乳腺癌患者中,不同分子亚型在年龄、肿瘤大小及临床分期方面无显著性差异,Basal-like型预后最差,分子分型是其独立预后指标。       

Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma: correlation with clinical outcome

The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.     

Distribution, clinicopathologic features and survival of breast cancer subtypes in Southern China

Breast cancer research and treatment by different subtypes is an inevitable trend. We investigated the clinicopathologic features and outcomes of different breast cancer subtypes in Southern China. A total of 5809 patients with invasive ductal carcinomas were identified. Immunohistochemical (IHC) markers for estrogen receptor (ER), progesterone receptor (PR), Her2/neu, and Ki‐67 proliferation index were used to classify cases into five molecular subtypes. Clinicopathologic characteristics and survival rates were analyzed retrospectively. Of all patients, 31.1% were luminal A subtype, 30.4% luminal B (high Ki‐67), 13.1% luminal B (Her2/neu+), 9.0% Her2/neu and 16.5% triple negative subtype. Luminal B (high Ki‐67) presented primarily in premenopausal patients with the lowest average age (43.0 years). Her2/neu positive tumors were more closely associated with aggressive features including increased tumor size, positive lymph node status and lymphvascular invasion (LVI). Triple negative subtype was characterized by poorer histologic grade. Her2/neu positive cases had presented the worst 5‐year disease‐free survival (DFS) and overall survival (OS). Multivariate analyses of OS and DFS suggested that there were different negative prognostic factors for the five subtypes. The benefit of the cyclophosphamide, methotrexate, and 5‐fluorouracil (5FU) (CMF) regimen was equal to that of anthracycline‐based and Taxane‐based regimens for patients with luminal A subtype and triple negative subtype, but inferior to anthracycline‐based and Taxane‐based regimens for those with two luminal B subtypes and Her2/neu subtype. The prognostic significance of traditional markers may differ among subtypes. This study revealed the distinct clinicopathologic characteristics, systemic therapy benefits, prognostic factors and survival rate among different breast cancer subtypes.