pT1期肺腺癌间质浸润的分级及预后意义

目的 探讨TNM病理分期T1(pathologic-T1,pT1)期肺腺癌中间质浸润分级的预后意义.方法 选择具有完整临床病理及随访资料结果 的pT1期肺腺癌85例,根据间质浸润在肿瘤中的部位将每例肿瘤中间质浸润的程度分为1-3级,分析各间质浸润级别病例的临床病理特征及预后.结果 间质浸润各级别肿瘤的病例数为1级:17例(20%),2级:12例(14%),3级:56例(66%).临床病理特征:肿瘤大小及淋巴血管侵犯率除1级病例小于3级病例(P值分别为0.005及0.018)外其余各级病例间的差异无统计学意义.淋巴结转移率及病理学分期在1级和2级病例完全相同并低于3级病例(1级与3级P值分别为0.007及0.002;2级与3级P值分别为0.027及0.021).性别、年龄及吸烟史各级病例间的差异无统计学意义.预后:本组病例5年总生存率是63%.1-3级病例的5年生存率分别为100%、83.3%及46.6%,2级与3级病例间的差异有统计学意义(P=0.027),随访期间病死率1-3级病例分别为0、16.7%及42.9%,1级与3级病例间的差异有统计学意义(P=0.001),而与2级病例间的差异无统计学意义.单因素预后分析提示间质浸润分级(P=0.001)、病理学分期(P<0.001)、淋巴血管侵犯(P<0.001)及淋巴结转移(P<0.001)与预后相关.多因素预后分析提示仅病理学分期(P<0.001)为独立预后因素.结论 间质浸润分级是一个与肿瘤预后及其他预后因素均密切相关组织学分级系统,它可作为pT1期肺腺癌预后分类的标准之一.     

术前诊断为子宫内膜不典型增生的子宫内膜癌患者的处理

目的分析和总结术前诊断为子宫内膜不典型增生的子宫内膜癌患者的临床特点及治疗方法。方法 2005年1月至2010年12月北京协和医院妇产科行全子宫切除术后病理诊断为子宫内膜样癌的患者共计404例,其中44例术前子宫内膜活检病理提示子宫内膜不典型增生(AEH),回顾性分析这些患者的临床特点,采用SPSS 13.0统计学软件进行分析。结果 44例术前诊断为AEH的患者中,39例(89%)患者未行子宫内膜癌分期术,子宫切除术后病理均为高分化子宫内膜样癌(100%),14例(32%)年轻患者保留了双侧卵巢,9例(20%)患者给予辅助放疗。中位随诊时间52个月,无复发病例。和绝经后患者相比,绝经前患者术后深肌层浸润(1/22及4/22)及淋巴血管间隙浸润(0/22及3/22)更少,但无统计学差异。比较AEH组和术前诊断为子宫内膜样癌的患者(EC组),AEH组高分化子宫内膜样癌的比例明显高于EC组(P=0.000);辅助化疗率和复发率明显低于EC组(P=0.003和0.019)。结论术前诊刮为AEH的子宫内膜癌患者预后好,年轻患者充分评估后可以考虑保留卵巢,绝经后患者AEH伴发子宫内膜样癌的风险增高,且更容易合并深肌层浸润、淋巴血管间隙受累等高危因素。     

Expression of prognostic factors (EGFR, ER) by immunohistochemical staining method in male breast cancer

Twelve male patients with operable breast cancer were evaluated for the expression of prognostic factors by immunohistochemical staining assay. Seven patients were stage I & II, and five patients were stage III. Axillary lymph node positivity was 42%. Nine patients were nuclear grade I, three were nuclear grade II, and none were nuclear grade III. The expression rate of EGFR (epidermal growth factor receptor), ER (estrogen receptor) were 8.3%, 70.0% respectively. This limited data suggest better tumor behavior in male than in female breast cancer. Adjuvant treatment should be considered in male breast cancer just as in females, based on axillary lymph node and ER states.     

基于多参数MR的影像组学融合模型术前预测宫颈鳞癌脉管浸润的应用价值

目的 探讨基于多参数MR的影像组学融合模型术前预测宫颈鳞癌脉管间隙浸润（LVSI）的应用价值。方法 回顾性研究。纳入2016年6月—2019年3月山西省肿瘤医院宫颈鳞癌患者168例。患者年龄22~76（52.0±10.1）岁,临床分期为国际妇产联盟（FIGO）ⅠB期127例、ⅡA期41例。所有患者术前行多参数盆腔MR扫描,均接受根治性子宫切除术联合盆腔淋巴结清扫术治疗。收集其临床病理资料和多参数MRI数据,以7∶3的比例按照随机抽样法分为训练集117例和验证集51例。在T₂加权像（T₂WI）、表观弥散系数[ADC,由2个b值的弥散加权成像数据自动生成]及增强T₁加权像（cT₁WI）3个序列的MRI上,对病灶进行手动分割勾画肿瘤轮廓感兴趣区（ROI）,得到三维感兴趣区（VOI）并提取特征,通过以最大相关最小冗余和最小绝对收缩与选择算子回归为主的三步降维法筛选特征并构建影像组学模型。多因素logistic回归分析筛选临床特征并联合影像组学模型建立融合模型,制作列线图。受试者操作特征曲线（ROC 曲线）、校正曲线、决策分析曲线评估列线图的效能及临床效益。结果 术后病理检查确诊LVSI阳性42例,阴性126例。训练集与验证集患者的年龄、FIGO分期、肿瘤最大径、肿瘤分化程度、LVSI状态等临床病理特征比较,差异均无统计学意义（P值均>0.05）。基于T₂WI、ADC及cT₁WI多参数MRI提取的影像组学特征,经特征筛选后得到7个关键特征,均与宫颈癌LVSI相关（P值均<0.05）,并构建影像组学模型。训练集T₂WI、ADC及cT₁WI 3个序列独立构建的影像组学模型预测宫颈癌LVSI的ROC曲线下面积（AUC）分别为0.630[95%可信区间（CI）0.557~0.698]、0.686（95%CI 0.563~0.694）、0.761（95%CI 0.702~0.818）,3个序列共同构建的联合影像组学模型对应的AUC为0.887（95%CI 0.842~0.925）,诊断效能最优,并在验证集中得到验证。联合影像组学模型与肿瘤分化程度构建的融合模型列线图预测宫颈癌LVSI,在训练集与验证集中的AUC分别为0.893（95%CI 0.851~0.929）、0.854（95%CI 0.749~0.943）,校正曲线显示出列线图有良好的校正性能;决策曲线表明当风险阈值概率范围在0.50~0.96时,采用影像组学融合模型预测宫颈癌LVSI的净收益优于“将所有患者视为宫颈癌LVSI阳性或阴性”。结论 基于多参数MRI影像组学特征与临床特征的融合模型对宫颈癌LVSI状态有良好的预测价值。     

Renal cell carcinoma in South Korea: a multicenter study

The incidence of renal cell carcinoma (RCC) in South Korea is steadily becoming similar to that in Western countries. This study summarizes the results of a 3-year multicenter survey of RCC in South Korea, conducted by the Korean Genitourinary Pathology Study Group. A total of 795 cases of RCC were collected from 20 institutes between 1995 and 1997, including 686 clear cell RCCs (86.3%), 58 papillary RCCS (7.30%), 49 chromphobe RCCs (6.16%), and 2 collecting duct RCCs (0.25%). At least 5 years of follow-up was available for 627 clear cell, 54 papillary, and 49 chromophobe RCCs. All subtypes presented most frequently with stage T3aN0M0 at the time of operation, and papillary RCCs demonstrated more frequent lymph node metastasis. Overall survival was not significantly related to the histological subtype (clear cell vs papillary, P = 0.8651; clear cell vs chromophobe, P = 0.0584; papillary vs chromophobe, P = 0.0743). For clear cell RCCs, statistically significant associations were found between overall survival and sex (P = 0.0153), multiplicity (P = 0.0461), necrosis (P = 0.0191), age, sarcomatoid change, TNM stage, nuclear grade, and modality of treatment (all P <0.0001). Overall survival was significantly associated with tumor size (P = 0.0307), nuclear grade (P = 0.0235), multiplicity, sarcomatoid change, and TNM stage (all P <0.0001) for papillary RCCs and with the presence of sarcomatoid change (P = 0.0281), nuclear grade (P = 0.0015), treatment modality (P = 0.0328), and TNM stage (P <0.0001) for chromophobe RCCs. Age (P = 0.0125), nodal stage (P = 0.0010), and treatment modality (P = 0.0001) were significant independent prognostic indicators for clear cell RCC on multivariate analysis. This is the first multicenter study of RCC in South Korea, demonstrating the general patterns and prognostic factors of Korean RCCs.     

Prediction of lymphovascular space invasion in patients with endometrial cancer

Objective: Predict the presence of lymphovascular space invasion (LVSI), using uterine factors such as tumor diameter (TD), grade, and depth of myometrial invasion (MMI). Develop a predictive model that could serve as a marker of LVSI in women with endometrial cancer (EC).Methods: Data from 888 patients with endometrioid EC who were treated between January 2009 and December 2018 were reviewed. The patients'' data were retrieved from six institutions. We assessed the differences in the clinicopathological characteristics between patients with and without LVSI. We performed logistic regression analysis to determine which clinicopathological characteristics were the risk factors for positive LVSI status and to estimate the odds ratio (OR) for each covariate. Using the risk factors and OR identified through this process, we created a model that could predict LVSI and analyzed it further using receiver operating characteristic curve analysis.Results: In multivariate logistic regression analysis, tumor size (P = 0.027), percentage of MMI (P < 0.001), and presence of cervical stromal invasion (P = 0.002) were identified as the risk factors for LVSI. Based on the results of multivariate logistic regression analysis, we developed a simplified LVSI prediction model for clinical use. We defined the “LVSI index” as “TD×%MMI×tumor grade×cervical stromal involvement.” The area under curve was 0.839 (95% CI= 0.809-0.869; sensitivity, 74.1%; specificity, 80.5%; negative predictive value, 47.3%; positive predictive value, 8.6%; P < 0.001), and the optimal cut-off value was 200.Conclusion: Using the modified risk index of LVSI, it is possible to predict the presence of LVSI in women with endometrioid endometrial cancer. Our prediction model may be an appropriate tool for integration into the clinical decision-making process when assessed either preoperatively or intraoperatively.     

A grading system combining architectural features and mitotic count predicts recurrence in stage I lung adenocarcinoma

The International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) has recently proposed a new lung adenocarcinoma classification. We investigated whether nuclear features can stratify prognostic subsets. Slides of 485 stage I lung adenocarcinoma patients were reviewed. We evaluated nuclear diameter, nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, prominence of nucleoli, intranuclear inclusions, mitotic count/10 high-power fields (HPFs) or 2.4?mm(2), and atypical mitoses. Tumors were classified into histologic subtypes according to the IASLC/ATS/ERS classification and grouped by architectural grade into low (adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic predominant), intermediate (papillary or acinar), and high (micropapillary or solid). Log-rank tests and Cox regression models evaluated the ability of clinicopathologic factors to predict recurrence-free probability. In univariate analyses, nuclear diameter (P=0.007), nuclear atypia (P=0.006), mitotic count (P<0.001), and atypical mitoses (P<0.001) were significant predictors of recurrence. The recurrence-free probability of patients with high mitotic count (≥5/10?HPF: n=175) was the lowest (5-year recurrence-free probability=73%), followed by intermediate (2-4/10?HPF: n=106, 80%), and low (0-1/10?HPF: n=204, 91%, P<0.001). Combined architectural/mitotic grading system stratified patient outcomes (P<0.001): low grade (low architectural grade with any mitotic count and intermediate architectural grade with low mitotic count: n=201, 5-year recurrence-free probability=92%), intermediate grade (intermediate architectural grade with intermediate-high mitotic counts: n=206, 78%), and high grade (high architectural grade with any mitotic count: n=78, 68%). The advantage of adding mitotic count to architectural grade is in stratifying patients with intermediate architectural grade into two prognostically distinct categories (P=0.001). After adjusting for clinicopathologic factors including sex, stage, pleural/lymphovascular invasion, and necrosis, mitotic count was not an independent predictor of recurrence (P=0.178). However, patients with the high architectural/mitotic grade remained at significantly increased risk of recurrence (high vs low: P=0.005) after adjusting for clinical factors. We proposed this combined architectural/mitotic grade for lung adenocarcinoma as a practical method that can be applied in routine practice.     

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival=28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors.     

Invasive micropapillary carcinoma of the breast: clinicopathological and immunohistochemical study

Invasive micropapillary carcinoma (IMPCa) of the breast refers to a unique variant of invasive ductal carcinoma, but its biological behavior has not been elucidated well. We analyzed 16 IMPCa cases (10 pure type, six mixed type). The incidence of IMPCa was 1.0% of all primary breast carcinoma. High nuclear grade (75.0%), as well as poorly differentiated histological grade (81.3%), was frequently seen. Lymph node metastases were evident in 92.9% of the examined cases, and about half of them showed more than 10 positive nodes. Comparison between serially experienced invasive ductal carcinoma, not otherwise specified (IDC-NOS), revealed that both high nuclear grade and poor histological grade were significantly more frequent ( P  < 0001), there was a lower frequency of positive estrogen receptor/progesterone receptor ( P  < 0.05, P  < 0.01), a higher frequency of HER-2 overexpression ( P  < 0.025), and more frequent lymph node metastases ( P  < 0.05) in IMPCa. The comparison between lymph node positive IDC-NOS did not show any statistically significant differences in frequency for positive p53, matrix metalloproteinase protein-2 (MMP-2), vascular endothelial growth factor (VEGF) or E-cadherin. However, IMPCa showed a significantly increased number of blood vessels counted by CD34 immunostains ( P  < 0.05). These results suggest that IMPCa is, at least, the same or more aggressive than lymph node positive cases of IDC-NOS. Hence, not only the high incidence of lymph node metastases but also distant, blood-borne metastases may be important.     

High nuclear protein kinase Cθ expression may correlate with disease recurrence and poor survival in oral squamous cell carcinoma

Protein kinase Cs play important roles in many biological processes and tumorigenesis. This study examined the expression of protein kinase Cθ and assessed its significance in patients with oral squamous cell carcinoma. Immunohistochemical staining was carried out to investigate the expression of protein kinase Cθ in 59 cases of oral squamous cell carcinoma. The results were correlated with clinical characteristics and outcome of patients. Diffuse cytoplasmic protein kinase Cθ was identified in 53 (89.8%) of the 59 oral squamous cell carcinoma cases, and the expression was not statistically associated with any clinicopathologic parameter. Twenty (40.7%) of the 59 oral squamous cell carcinoma cases exhibited nuclear expression of protein kinase Cθ with different grade of intensity. χ(2) analysis indicated that high nuclear protein kinase Cθ expression correlated significantly with shorter 24-month survival (P = .043) and disease recurrence (P = .019). The Kaplan-Meier method also showed that high nuclear expression of protein kinase Cθ was significantly associated with poor overall survival (P = .034) and shorter time to recurrence (P = .003). Univariate analysis revealed that high nuclear protein kinase Cθ expression (P = .046; hazard ratio, 2.2), tumor size less than 2 cm (P = .049; hazard ratio, 4.7), lymph node metastasis (P = .003; hazard ratio, 3.0), and higher stage (P = .002; hazard ratio, 8.7) were each associated with shorter overall survival. We identified the aberrant nuclear expression of protein kinase Cθ in oral squamous cell carcinoma. High nuclear protein kinase Cθ expression may correlate with disease recurrence and poor survival in patients with oral squamous cell carcinoma.     

Estimation of tumor stage and lymph node status in patients with colorectal adenocarcinoma using probabilistic neural networks and logistic regression.

Staging colorectal adenocarcinoma on the basis of biopsy specimens could identify patients who might benefit from neoadjuvant therapy without undergoing resection first. In this study, we evaluated the ability of artificial neural networks with genetic algorithms and multivariate logistic regression to predict the stage of 99 patients with primary colorectal adenocarcinoma by analyzing age, tumor grade, and immunoreactivity to p53 and bcl-2 with use of endoscopically obtained biopsy specimens. We correlated results with regional lymph node status and tumor stage, identified in subsequent colectomy specimens. bcl-2 and p53 protein expression were demonstrated by immunohistochemical methods, using formalin-fixed, paraffin-embedded biopsy tissues. Tumor grade was evaluated in hematoxylinand eosin-stained sections. Patients were divided into training (n = 75) and testing cases (n = 24). Several probabilistic neural networks with genetic algorithm models were trained, using the four prognostic features as input neurons and regional lymph node status or stage as output neurons. Data were analyzed with univariate statistics and multivariate logistic regression. The cases were divided into training (n = 40) and testing (n = 59). The best two models classified correctly the lymph node status of 20 of 24 test patients (specificity, 80%; sensitivity, 85%; positive predictive value, 86%) and the tumor stage of 21 of 24 test patients (specificity, 82%; sensitivity, 92%; positive predictive value, 85%), respectively. Tumor grade and p53 protein were statistically significant (P < .05) by analysis of variance for lymph node status and tumor stage. Logistic regression models with these two independent variables correctly estimated the probability of lymph node metastases in 44 of 59 test cases and the tumor stage of 43 of 59 test cases, respectively. Results indicated the usefulness of probabilistic neural networks in the population studied, but the findings should be validated with large groups of patients.     

乳腺浸润性微乳头状癌的病理学特征与淋巴结转移的关系

目的研究乳腺浸润性微乳头状癌(IMPC)的病理学特征与淋巴结转移的关系。方法观察51例乳腺IMPC的主要病理学特征及淋巴结转移情况,采用免疫组织化学方法(LSAB法)检测IMPC中血管内皮生长因子(VEGF)-C和VEGF受体(R)-3的表达并计数淋巴管密度,分析其与淋巴结转移的关系。结果(1)乳腺IMPC病理组织学分级Ⅱ、Ⅲ级组的淋巴结转移数平均12.5个,明显高于Ⅰ级组的4.0个;(2)间质淋巴细胞浸润(+)和(++)组的淋巴结转移率(27/28,96.4%)明显高于(-)和(±)组(14/23,60.9%),且其淋巴结转移数平均14.4个,也明显高于(-)和(±)组的4.6个;(3)IMPC肿瘤细胞的VEGF-C表达在病理组织学分级Ⅱ、Ⅲ级组显著高于Ⅰ级组(P=0.03),VEGF-C的表达与淋巴结转移呈正相关(P=0.006);淋巴管密度与VEGF-C表达(P=0.009)、淋巴结转移(P=0.007)呈正相关;(4)肿瘤组织中IMPC成分的多少与淋巴结转移无显著性关系,淋巴结转移灶为纯IMPC或以IMPC成分为主;(5)28例伴有导管原位癌的IMPC中,14例为微乳头状型导管原位癌(14/28,50%)。结论乳腺IMPC的病理组织学分级、淋巴管密度及间质淋巴细胞浸润可能是影响IMPC淋巴结转移的关键性因素。VEGF-C和VEGFR-3表达增高是促使IMPC发生淋巴结转移的重要原因。微乳头状型导管原位癌可能是IMPC的早期阶段。     

PLAC1/CP1基因在原发结直肠癌组织中的表达及临床意义

目的 探讨PLAC1/CP1基因在原发结直肠腺癌组织中的表达及意义.方法 通过组织芯片和免疫组织化学检测PLAC1/CP1基因在97例结自肠腺癌配对癌组织、癌旁组织中的蛋白表达.结果 PLAC1/CP1基因在97例原发结直肠腺癌组织中的表达率为56.7%(55/97).PLAC1/CP1蛋白的胞核表达率为27.8%(27/97),胞质表达率为43.3%(42/97).女性患者的PLAC1/CP1蛋白胞核表达率显著高于男性患者(x2=6.567,P=0.010).PLAC1/CP1蛋白的胞核表达率随组织学分化程度的降低而升高(x2=8.321,P=0.016);TNM Ⅲ+Ⅳ期的胞核表达率明显高于Ⅰ+Ⅱ期(x2=18.726,P=0.000);有淋巴结转移的原发灶的胞核表达率明显高于无淋巴结转移的病灶(x2=17.407,P=0.000),随淋巴结转移灶数日的增多,胞核表达率升高(x2=22.632,P=0.000).结论 PLAC1/CP1蛋白在原发结直肠腺癌组织中的表达率高,细胞核定位表达与原发结直肠腺癌的组织学分化程度、TNM分期、淋巴结转移及转移程度有关,证明CP1基因在结直肠癌中具有较高的免疫原性,是结直肠癌较理想的免疫治疗靶点.

Abstract：

Objective To study the expression and significance of PLAC1/CP1 genes in patients with primary colorectal carcinoma. Methods The expression of PLAC1/CP1 genes in 97 cases of colorectal carcinoma was studied using tissue chip technology and immunohistochemistry. Results The rate of PLAC1/CP1 proteins expression in the cases studied was 56. 7% (55/97), with 27. 8% (27/97) being nuclear staining and 43. 3% (42/97) being cytoplasmic staining. The percentage of expression was higher in women than in men (x2 = 6. 567, P= 0.010). The expression in poorly differentiated colorectal carcinoma was significantly higher than that in the well or moderately differentiated carcinoma (x2 =8. 321,P =0. 016). The expression was also significantly higher in stage TNM Ⅲ or Ⅳ tumors than in stage TNM Ⅰ or Ⅱ tumors ( x2 = 18. 726, P =0. 000). The rate was higher in cases with lymph node metastasis than in those with negative lymph nodes ( x2 = 17. 407, P =0. 000), and was higher as the number of metastasisincreasing (x2 = 22. 632, P = 0. 000). Conclusion The expression of PLAC1/CP1 genes correlates with various clinical and pathologic parameters. It carries prognostic significance and may represent a potentialtarget for immunotherapy.     

Encapsulated papillary carcinoma of breast; a clinicopathological study of 25 cases and literature review with emphasis on high grade variant

Encapsulated Papillary Carcinoma (EPC) is a rare breast tumor with excellent prognosis. Treatment and stage of EPC is influenced by invasion and high nuclear grade. Our aim was to study the clinicopathological features of EPC, especially high grade tumors and to compare the features of invasive and non-invasive tumors.We reviewed clinicopathological features of 25 cases of EPC diagnosed at our institution from 2006 till 2020. Patients' age ranged from 21 to 75 years (median 55 years). Tumor size ranged from 1 to 9 cm (median 3.5 cm). Overall, invasion was present in 44% cases. High nuclear grade was observed in 24% cases. Majority of these high grade tumors were below 40 years. All of these tumors were 4 cm or larger in size. Two third of these tumors were invasive. Hormone receptor negativity and lymph node involvement was observed in 1 out of 3 cases, when performed. Clinicopathological and histological features of invasive and non-invasive tumors were compared and only lymph node involvement was found to be significantly more frequent in invasive tumors (p = 0.049). Median follow up duration was 18 months. All patients were alive and disease free except for a single patient who died of cerebrovascular accident.EPC has excellent clinical course. Invasion and high nuclear grade should be carefully searched for as these features determine tumor stage and treatment.     

Breast cancer in young women: clinicopathologic correlation.

It has been suggested that early-onset breast carcinomas may be different from those that occur in older women. The clinicopathologic characteristics of 191 young female patients (under 40 years of age) diagnosed with breast carcinoma (BC) were studied. Clinical history, staging, treatment and outcome were reviewed. Histology was assessed for tumor subtypes, invasive and in situ components, nuclear and histologic grades and lymph node status. Adjacent nontumoral breast tissue was evaluated. Clinically, 11 patients were stage 0, 21 stage I, 94 stage II, 38 stage III, 6 stage IV, and in 21 no information was obtained. Sixty five percent of patients had positive lymph nodes at diagnosis; 102 patients (54%) relapsed at a median of 29 months after diagnosis. Histologically, 180 cases were infiltrating BC, 150 ductal (83%), 19 lobular (11%) and 11 of special types (6%); 11 cases were ductal carcinoma in situ. We found no cases of medullary carcinoma. High nuclear grade and vascular invasions were frequent (68% and 67%, respectively) even in patients who remained disease-free at least 5 years after diagnosis (61% and 60%, respectively). Our study demonstrates that the histologic types of early-onset breast cancer are not different from other BC. However, BC in young women is often associated with histologic features of high-grade malignancy even in patients with better survival. Our results suggest that BCs in young women are different from those that occur in older women.     

Predicting sentinel lymph node metastases in infiltrating breast carcinoma with vascular invasion

Sentinel lymph node and clinically negative axillary node status was compared with well-known clinicopathological characteristics such as tumor size, histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER-2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph nodes were found in 29 of 100 patients: 19 with metastases detected by hematoxylin and eosin staining and 10 with micrometastases confirmed by immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present in larger carcinomas (P < 0.03), more frequently in tumors with negative PR status (P < 0.037) and evident lymphovascular invasion (P < 0.002). Lymphovascular invasion was also associated with breast cancer of higher histologic (P = 0.011) and nuclear grade (P = 0.039). Tumor size and the presence of lymphovascular invasion were found to be significant predictors of pathologically positive sentinel lymph node in T1 and T2.     

Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H-score with pathological parameters

The results of H-scores of oestrogen and progesterone receptor (ER and PR) expression in 150 invasive breast cancers were correlated with conventional pathological prognostic parameters: tumour size, histological grade and subtype, lymph node status, lymphovascular invasion, Nottingham Prognostic Index (NPI) and pathological stage. ER and PR status was determined by immunohistochemical staining of sections cut from archival paraffin-embedded tissue blocks. We defined positive receptor expression as a H-score of 50 and above. Our findings revealed ER and PR positivity in 98 (65%) and 52 (35%) cases, respectively. Fifty-one (34%) ER-positive cases also showed PR expression, while 51 (34%) tumours were negative for both ER and PR. Positive expression for ER and PR was significantly correlated with histological grade (P < 0.0005), mitotic score (P < 0.05) and nuclear pleomorphism (P < 0.05). When we used the relatively simpler method of a cut off of at least 10% tumour cell nuclear staining of moderate or greater intensity as positive receptor status, we found that it agreed well with results of the H-score, a more quantitative method of assessment.     

Primary gastrointestinal B-cell lymphoma. A clincopathological and immunohistochemical study of 61 cases with an evaluation of prognostic parameters.

We hereby present a retrospective clinicopathological and immunohistochemical study of surgically resected primary gastrointestinal (GI) lymphoma with an analysis of parameters of potential prognostic relevance. From a larger series of 144 cases of primary GI lymphomas, we chose 61 cases with sufficient clinical follow-up (mean 60, range 1-219 months), classified either as extranodal marginal zone B-cell lymphoma of MALT type (MALT lymphoma) or diffuse large B-cell lymphoma (DLBCL), after having excluded other subtypes. In addition to conventional clinical and morphological parameters, the expression levels of Ki-67 (MIB-1), bcl-2 and p53 were evaluated for prognostic significance. Twenty-one (34.4%) cases were classified as pure low grade marginal zone B-cell lymphoma of MALT type, 12 (19.7%) cases as low grade MALT lymphoma with a high grade component (mixed type), and 28 (45.9%) cases as primary extranodal DLBCL. Most of the lymphomas (53/61; 86.9%) were localized in the stomach, 3 (4.9%) in the small bowel, 3 (4.9%) multifocal in both stomach and small intestine and 2 (3.3%) in the large bowel. MIB-1 expression in more than 30% of tumor cells was detected in 42 (68.6%), bcl-2 expression in 20 (32.8%) and p53 accumulation in more than 10% of neoplastic cells in 16 (26.2%) lymphomas. Both high Ki-67 expression and p53 accumulation were more prevalent in the DLBCL. 30 (49%) patients showed lymph node involvement at surgery, 14 (23%) patients suffered tumor recurrence, and 24 (38.5%) died during the follow-up period. Tumor recurrence occurred primarily in patients who had presented lymph node involvement (9/14, 64.3%). The 5-year survival rate was 66.1% for all patients. Important prognostic factors for overall survival were tumor stage (p < .004) and p53 accumulation (p < .05) in univariate analysis, and tumor stage in multivariate analysis (p < .001). Although p53 accumulation did not reach statistical significance in our small study group, it may be both important in the transformation of low grade MALT lymphoma and an indicator for aggressive behavior in high grade tumors.     

Topoisomerase I protein expression in primary colorectal cancer and lymph node metastases

Topoisomerase I (topo I) is an important target for the treatment of malignant disease, especially colorectal cancer. Because there is little information on the expression of topo I in colorectal tumors, this study evaluated and characterized topo I protein expression in primary colorectal cancer and lymph node metastases and studied the association between topo I protein expression and clinicopathologic data, p53 status, and proliferating cell nuclear antigen (PCNA) status. Immunohistochemistry assay was performed for topo I protein expression in 249 primary human colorectal cancer and 42 paired lymph node metastasis samples. Topo I expression was described as the percentage of cells staining positive for topo I, along with the intensity and localization of the staining. Clinicopathologic data (sex, age, Dukes' stage, differentiation grade, survival status), p53 status, and PCNA status were statistically analyzed for association with topo I protein expression. Topo I expression in paired primary lymph node metastases were studied for concordance. Topo I protein expression was detected in 127 (51%) samples, including 24.4% with >50% positive tumor cells. The majority had nuclear (70.1%) or nuclear and cytoplasmic staining (17.3%). A higher percentage of cells expressing topo I in primary colorectal cancer was significantly associated with advanced age (P =.040). Patients with rectal cancer had greater topo I expression than those with colon tumors (P =.029). No significant correlation was found between topo I protein expression and sex, Dukes' stage, differentiation grade, survival status, p53 status, and PCNA status. Concordance in topo I staining between primary and lymph node metastases was observed in 33 of 42 cases (P =.029). This suggests that the activity of topo I inhibitors will not differ across various tumor stages, pathology, and patient gender. p53 and PCNA status do not appear to influence topo I expression, and topo I has no apparent association with the acquisition of a metastatic phenotype. Topo I expression now needs to be evaluated in patients undergoing topo I-inhibitor therapy, to better define the role of this protein as a predictive marker.     

Immunohistochemical markers of cell cycle control applied to ovarian and primary peritoneal surface epithelial neoplasms: p21(WAF1/CIP1) predicts survival and good response to platinin-based chemotherapy.

Immunohistochemistry for p53, p21(WAF1/CIP1), and Ki-67 provides insight into the molecular events controlling the cell cycle. We tested the hypothesis that these cell cycle markers will aid in the clinical evaluation of ovarian and primary peritoneal surface epithelial neoplasms (SENs). Paraffin sections from a retrospective surgical series of 117 SENs were immunostained with anti-p53 (clone DO7, Novacastra Laboratories, UK), anti-p21(WAF1/CIP1) (clone EA10, Oncogene Science, Cambridge, MA), and anti-Ki-67 (clone MIB-1, Immunotech, Westbrook, ME). The Ki-67 proliferation index (Ki-67PI) and immunoreactivity were evaluated. One hundred seventeen SENs reacted as follows: p53 50%+ and p21(WAF1/CIP1) 65%+. Ki-67PI ranged from 4% to 88% (mean/median = 44/46%). p53 reactivity associated with transitional cell histology, decreased p21(WAF1/CIP1) staining, increased Ki-67PI, architectural/nuclear grade, and stage (P < .05, 1 x 10(-7), .01, .05/.0001, .001,). p21(WAF1/CIP1) staining was associated with endometrioid/clear cell histology, decreased Ki-67PI, architectural/nuclear grade, and stage (P < 05/.05, .05, .01/1 x 10(-8), 1 x 10(-5)). Ki-67PI associated with increased architectural/nuclear grade but not mucinous histology (P < 1 x 10(-5)/1 x 10(-6), .01). Sixty-seven patients had disease at last follow-up; 53 were dead of disease at 0 to 67 months (mean/median, 21/18), and 14 were alive with disease at 12 to 224 months (mean/median, 56/40). Fifty patients were disease free at 5 to 214 months (mean/median, 59/41). Predictors of survival include decreased Ki-67PI, stage, architectural/nuclear grade (P < 1 x 10(-6), 1 x 10(-10), 1 x 10(-10)/.005) and p21(WAF1/CIP1) IMS (multivariate P < 1 x 10(-6)). p21(WAF1/CIP1), a potent inhibitor of cyclin-dependent kinases necessary for cell cycle progression, functions as a key checkpoint in cell cycle control. Immunoreactivity for p21(WAF1/CIP1) provides prognostic information independent of other histological and clinical predictors, p53 IMS, and Ki-67PI in this series of 117 PTs with SENs. Our preliminary data suggest an interrelationship between p21(WAF1/CIP1) expression and an effective clinical response to platinin-based chemotherapy, both associated with apoptosis. Further investigation seems warranted.