192例浸润性乳腺癌导管内扩散及预后因素分析

目的：探讨浸润性乳腺癌导管内扩散的形态特征及其与组织学分级、c-erbB-2过表达及脉管累犯的关系。方法：对192例浸润性乳腺癌的导管内扩散情况及其与组织学分级、c-erbB-2过表达及脉管累犯的关系进行统计分析。结果：192年浸润性乳腺癌中，导管内扩散阳性88例（45．8％），其中脉管累犯阳性组中，导管内扩散阳性率为56．6％，明显高于脉管累犯阴性组（34．4％），且差异有显著性（P＜0．005）。导管内扩散阳性组中，c-erbB-2阳性率为72．7％，高于导管内扩散阴性组（54．8％），且差异有显著性（P＜0．025）。导管内扩散与组织学分级呈正相关（P＜0．05）。结论：导管内扩散与组织学分级、c-erbB-2过表达及脉管累犯呈现正相关，浸润性乳腺癌中伴导管内扩散者更具有侵袭性和转移性。     

乳腺导管原位癌组织学分级与其他预后因素的关系

目的　探讨乳腺导管原位癌组织学分级与分型以及ｃｅｒｂＢ２ 蛋白、ｐ５３ 蛋白、ＭＩＢ１ 、雌激素受体（ＥＲ） 表达的关系,以期为临床判断潜在恶性程度及预后提供参数。方法　参照Ｖａｎ Ｎｕｙｓ 分类方法,对３２ 例乳腺导管原位癌按核的分级、有无坏死进行组织学分级,并将标本行ｃｅｒｂＢ２ 蛋白、ｐ５３ 蛋白、ＭＩＢ１、ＥＲ的枸橼酸微波ＡＢＣ免疫组化法染色。结果　Ⅰ级（分化好）１２ 例（３７．５％ ） ,Ⅱ级（中度分化）９ 例（２８．１％ ） ,Ⅲ级１１ 例（３４．４％ ）。Ⅲ级患者中,９ 例为粉刺型,１ 例为微乳头状型,１ 例为实体型,Ⅲ级的ｃｅｒｂＢ２、ｐ５３ 和ＭＩＢ１ 蛋白表达的阳性率分别高于Ⅱ级和Ⅰ级,并与Ⅰ级比较差异有显著意义（ Ｐ＜０．０５） ,ＥＲ阳性率低于Ⅱ级和Ⅰ级。结论　乳腺导管原位癌Ｖａｎ Ｎｕｙｓ 组织学分级可能是一个较好的预后指标。     

乳腺浸润性筛状癌临床病理分析

目的探讨乳腺浸润性筛状癌（invasive cribriform carcinoma,ICC）的临床病理和免疫表型特点。方法复习8例乳腺ICC的临床病理资料,并将其组织学特征、免疫表型和预后与浸润性导管癌进行比较。结果乳腺ICC发病平均年龄42．9岁,多表现为无痛性乳房肿块,影像学微钙化常见。组织学特征是不规则癌细胞团巢呈筛状结构浸润性生长,瘤细胞核级低-中等,多数病例核分裂象少见,胞质顶浆分泌和间质成纤维细胞增生易见,常并存筛状型导管原位癌和小管癌。免疫表型显示CK34βE12高表达而CK5／6阴性,肌上皮标记阴性。8例中经典型6例、混合型2例,其发病年龄、组织学分级、腋淋巴结转移率、c-erbB-2和Ki-67阳性率均低于浸润性导管癌,近期随访结果显示预后优于浸润性导管癌。结论乳腺ICC作为WHO新确定的浸润性癌类型,预后较好,需要与筛状型导管原位癌和腺样囊性癌等鉴别,免疫组化染色有助于确诊。     

乳腺浸润性导管癌与小叶癌的超声诊断分析

目的探讨乳腺浸润性导管癌和浸润性小叶癌的超声声像图特征。方法对2006年1月至2008年6月经手术、病理证实为乳腺浸润性导管癌（IDC）136例和浸润性小叶癌61例的超声声像图、彩色多普勒表现进行对比分析。结果两种病理类型的肿瘤的超声声像图在肿块形状、内部与后方回声以及血流图上差异有统计学意义（P〈0．05）。在侧方回声与内部钙化情况上差异无统计学意义（P〉0．05）。结论乳腺浸润性导管癌和浸润性小叶癌可以根据各自超声声像的特点进行诊断，组织学的不同影响乳腺癌的超声影像表现。     

乳腺癌预后与肿瘤基因Her—2／neu的研究

通过对１４３例乳膛癌病例追踪观察，证明５年内死亡组（高危组）Ｈｅｒ－２阳性率远高于五年后仍生存的病例（低危组），两者间差异有显著性。在浸润性导管癌阳性率为３３％，分化愈低则阳性率愈高，组织学类型与阳性率有关；粉刺癌阳性率最高而小叶癌最低。阳性率与固定液的选择及标准的掌握有关。我们认为应以单克隆抗体胞膜着色作为阳性标准。Ｈｅｒ－２／ｎｅｕ可作为传统乳腺癌预后指标的一个补充。     

乳腺癌组织中金属硫蛋白表达的意义

目的：探讨金属硫蛋白（ＭＴ）在浸润性乳腺导管癌中的表达及其临床意义。方法：常规免疫组化ＬＡＢ法检测了９６例浸润乳腺导管癌术后标本中ＭＴ中的表达情况。结果：浸润性乳腺导管癌标本的表达率为５２．１％,在大多数阳性病例中胞浆、胞核均着色。ＭＴ表达与乳腺癌的核分级有关;ＭＴ表达阳性者和阴性者相比预后大多较差。结论：ＭＴ表达可预测癌的预后,ＭＴ有可能作为又一个增殖旺盛、侵袭强的肿瘤标志物。     

转化生长因子β1和β3在前列腺癌的表达及意义

一、材料与方法１标本：选用我院１９８６～１９９６年间前列腺癌４６例，年龄５３～８４岁，平均６８２±９１岁。组织学分级（Ｇｌｅａｓｏｎ标准）：２～５分（高分化）２５例，６～８分（中分化）１９例，９～１０分（低分化）２例。临床分期（Ｊｅｗｅｔｗｈ...     

CD44v4在乳腺浸润性导管癌中的表达及 其与浸润转移的关系

目的 探讨CD44v4在浸润性乳腺导管癌中的表达及其与浸润转移的关系。方法 选取2011年1月~2018年3月我院收治的乳腺浸润性导管癌185例设为观察组,另选取同期收治的乳腺良性疾病患者60例设为对照组,采用免疫组化法检测两组CD44v4的表达情况,并比较观察组CD44v4表达及临床病理因素情况。结果 观察组CD44v4阳性表达率为60.54%,高于对照组的5.00%,差异有统计学意义（P＜0.05）。CD44v4表达在不同年龄、绝经前后月经状况、原发瘤大小间比较,差异无统计学意义（P＞0.05）;不同TNM分期、组织学分级、淋巴结转移患者的CD44v4表达比较,差异有统计学意义（P＜0.05）。结论 CD44v4蛋白在乳腺浸润性导管癌患者中为高表达,检测其表达可作为判断肿瘤预后的新指标。     

泛素连接酶hHrd1在人乳腺癌组织表达的意义

目的探讨一种泛素连接酶hHrd1在人乳腺癌发病中的病理意义。方法应用免疫组织化学SP法研究正常人乳腺组织、乳腺增生症、乳腺纤维腺瘤、原发性乳腺癌组织中hHrd1的表达。结果人乳腺癌组织hHrd1蛋白表达水平明显强于正常人乳腺组织、乳腺增生症、乳腺纤维腺瘤。导管内癌（或伴早浸）与浸润性导管癌相比，表达水平低，差异有显著性意义（P〈0．05）。人乳腺浸润性导管癌组织hHrd1表达与肿瘤大小有关（P〈0．05），与组织学分级、淋巴结是否转移无关（P〉0．05）。结论泛素连接酶hHrd1参与人乳腺癌的发生。     

结直肠癌脆性组氨酸三联体蛋白表达丢失研究

目的 探讨结直肠癌中脆性组氨酸三联体（FHIT）基因蛋白表达状况及其与临床病理指标的可能关系。方法 采用兔抗人FHIT蛋白抗体和枸橼酸－微波－SP免疫组织化学方法检测60例甲醛固定、石蜡包埋的结直肠癌蜡块标本中FHIT表达状况并分析其与组织学分级、Dukes分期以及5年生存率的关系。结果 癌组织FHIT表达强度较正常黏膜高者为21例（35．0％）,较正常黏膜低者为33例（55．0％）,与正常黏膜基本相等者为6例（10．0％）。FHIT蛋白低表达癌在癌组织学分级中的分布为I级癌7／16,Ⅱ级癌14／30,Ⅲ级癌12／14,各级癌组间比较,差异有显著性（P＜0．05）。FHIT蛋白低表达癌在Dukes分期中的分布为A组癌5／11,B期癌12／28,C期癌16／21,已伴淋巴结转移组的C期癌与未转移组的A、B期癌比较,差异有显著性（P＜0．05）。39例获访病例中,FHIT蛋白低表达癌在5年随访病例组中的分布为5年生存组为13／25,5年死亡组为12／14,组间比较差异有显著性（P＜0．05）。结论 结直肠癌FHIT表达状况可能与组织学分级、Dukes分期以及5年生存率相关,提示FHIT表达降低可能对结直肠癌的演化和进展具有一定重要作用,并可能成为一个新的预后指标。     

Study of grading of urothelial carcinoma in transurethral resection of urinary bladder tumor specimens

This study is conducted to evaluate prognostic significance of recently introduced WHO (World Health Organization) 1999 grading system for urothelial carcinoma on transurethral resection of urinary bladder tumor (TURBT) specimens reported during the period from 1996 to 2000. Progression free survival estimates were obtained by Kaplan-Meier method on SPSS software with log rank test application. Among 70 cases, progression occurred in 38 patients from which grade I were 3, grade II were 11 and grade III were 24. The mean period from diagnosis to progression was 76.8, 19.2 and 3.5 months for grade I, II, III respectively. The progression free survival rates at one year were 100% for grade I, 42% for grade II and 5% for grade III. (Log rank test: p < 0.001). WHO 1999 grading system can classify urothelial carcinomas into prognostically different groups, which is statistically significant.     

Heterogeneity of invasive ductal carcinoma: proposal for a hypothetical classification

To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time.     

Fine‐needle aspiration of renal cell carcinoma: Is accurate Fuhrman grading possible on cytologic material?

The Fuhrman grading system of renal cell carcinoma (RCC) consists of four grades based on nuclear size/contour and nucleolar conspicuousness. Fuhrman grading of histpathologic material is an independent prognostic parameter for RCC. Although widely used in surgical pathology, Fuhrman grading is not routinely performed on cytologic material. Thirty-three cases of renal fine needle aspirations (FNAs) with histologically proven RCC were retrieved from the cytopathology archives at Johns Hopkins Hospital. Fuhrman grade was determined independently and blindly by three faculty cytopathologists and compared with the Fuhrman grade of the subsequent surgical pathology specimen. The 33 resection specimens had the following Fuhrman grades: 0/33, grade I; 24/33 (73%), grade II; 9/33 (27%), grade III; and 0/33, grade IV. After Fuhrman grading was applied to the FNA material, diagnostic sensitivity was 83% for grade II versus 44% for grade III. The specificity and accuracy were 50 and 75%, respectively, for grade II versus 100% and 84% for grade III. Diagnostic sensitivity for grade II tumors ranged from 38 to 83%, grade III 44-62%. Diagnostic specificity for grade II tumors ranged from 50 to 78%, grade III 80-100%. Accuracy ranged from 48 to 75% for grade II and 75-87% for grade III. Using a two-tier grading model, accuracy improved to 84.2%. In our experience, Fuhrman grading of FNA specimens yielded variable results. There was only moderate agreement between cytopathologists, with an overall tendency to undergrade the tumor when compared with the resection specimen. Averaging the participants' grading and using a two-tier instead of four-tier system improved overall performance.     

Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters

Objective: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters. Methods: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III). Results: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages. Conclusions: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.     

Ki-67 reactivity in primary fallopian tube cancers

Forty-four cases of primary cancer of the fallopian tube (PFTC) were analyzed as to Ki-67 expression, grade, stage and the cancer histological type. Among patients with an average age of 57.5 years (range 38-70 years), 27 patients were FIGO I, 7 were FIGO II and 10 were FIGO III. Histological classification of PFTC revealed 18 cases of endometrioid type, 9 serous, 7 undifferentiated, 6 urothelial, 2 clear-cell and 2 of other type. Histological grading revealed 11 cases of G1, 16 of G2 and 17 of G3 tumors. The quantity of Ki-67 positive cells was counted on 300 cancer cells in random high-power fields (10 x 40) and recorded as the labeling index (LI, %). Positive staining for Ki-67 was shown in the nuclei in all cases. Ki-67 LI values ranged from 14.2 to 97.2% (median 36.1). Ki-67 LI values were graded as > or = 36.1% as high and <36.1% as low. We did not find any significant differences in Ki-67 LI values among tumors of various clinical stages, histological grades and histological types. The p value was statistically significant only for stage as a prognostic factor.     

Accuracy of cytological grading of spindle-cell sarcomas

Spindle-cell sarcomas constitute an important component of soft-tissue sarcomas, where accurate grading may be more important than histologic subtype in order to plan treatment strategies and determine prognosis. To evaluate the applicability and accuracy of grading spindle-cell sarcomas on fine-needle aspiration cytology (FNAC) smears, 54 cases of histologically documented spindle-cell sarcomas, consisting of synovial sarcomas (20 cases), neurofibrosarcomas (12 cases), leiomyosarcomas (9 cases), dermatofibrosarcoma protuberans (DFSP; 6 cases), fibrosarcomas (3 cases), hemangiopericytomas (2 cases), and spindle-cell sarcomas, unclassified (2 cases), were graded according to a three-tier system proposed earlier for FNAC smears, while the histological sections were graded using the French Federation of National Cancer Centers (FNCLCC) grading system. The cytological grading was correlated with the histological grade. There was an overall cytologic and histologic concordance in 40/54 (74%) cases, and concordance in 9/13 (69%) grade I, 19/25 (76%) grade II, and 12/16 (75%) grade III cases. Analysis of grading of individual sarcomas revealed a concordance in 92% of neurofibrosarcomas, 78% of leiomyosarcomas, 70% of synovial sarcomas, 67% of dermatofibrosarcoma protuberans, 67% of fibrosarcomas, 50% of hemangiopericytomas, and 50% of cases of malignant mesenchymal tumors, spindle-cell type unclassified. Major noncorrelation was seen in 10/54 (18.5%) cases. Minor noncorrelation was seen in 4/54 (7.4%) cases. Thus it is possible to accurately predict the grade in 74% of cases of spindle-cell sarcomas. The cytological and histological concordance was better (75%) in high-grade (grades II and III) as compared to grade I sarcomas (69%). Sampling errors due to morphologic heterogeneity in sarcomas may cause noncorrelation in a few cases.     

Histological grading and prognosis in dogs with mammary carcinomas: application of a human grading method

The human "Elston and Ellis grading method" was used in dogs with mammary carcinoma to examine its relation to prognosis in this species, based on a 2-year follow-up period. Of the 85 cases examined, 27(31.8%) had well-differentiated (grade I), 28 (32.9%) had moderately differentiated (grade II) and 30 (35.3%) had poorly differentiated (grade III) carcinomas. Two years after mastectomy, significant differences in survival between cases with different tumour grade were found; thus, survival was worse in dogs with grade III carcinomas than in those with grade II (P<0.05) or grade I (P<0.001) tumours. However, in dogs with simple carcinomas which had a less favourable prognosis than that of other carcinomas (P<0.001), there was no significant difference in survival between grade II and grade III cases (P=0.878), both having a very poor prognosis. Undifferentiated (grade III) carcinoma cases had a 21-fold increased risk of death as compared with differentiated (grade I and II) carcinoma cases. An increased risk (about 10-fold) was also associated with undifferentiated simple carcinomas as compared with differentiated ones. The predictive value of histological grade was not influenced by tumour size or age of the dog at mastectomy; nodal metastasis, however, worsened the prognosis (P<0.001). Routine use of this human grading method would help the clinician to make a more accurate prognosis in the interests of post-surgical management in dogs with mammary carcinomas.     

Grading ductal carcinoma in situ of the breast using an automated proliferation index

Tumor grade, size and margin status are the most significant factors in predicting the behavior of ductal carcinoma in-situ (DCIS). The inclusion of necrosis and nuclear grade in the grading of DCIS has demonstrated a fair but suboptimal agreement between pathologists. The grading of DCIS was studied and compared to the Van Nuys (VN) system, by using our newly proposed unifying "nuclear grade + proliferation index (N+P) grading system for invasive carcinomas. 162 DCIS tumors were studied including 49 VN I, 31 VN II, and 82 VN III cases. The VN and N+P systems were compared with each other and correlated with tumor size, ER, PR, p53, Her-2, EGFR, Bcl-2, p27 and p21 status. The two systems demonstrated similar frequencies for the different grades and an agreement with each other for all of the biomarkers studied. The greatest difference between the two systems was observed for those tumors initially classified as VN II (94% being down-graded to N+P I) and VN III (80% being down-graded to N+P II). These results suggest that the N+P system, combining nuclear grade with automated MIB-1 count, is a potentially valid and reproducible grading system for both non-invasive and invasive mammary carcinomas. It is automated, less subjective in assessing mitotic activity and necrosis and correlates with other prognostic biomarkers.     

Clinicopathological relevance of tumour grading in canine osteosarcoma

Tumour grading assesses biological aggressiveness and is of prognostic significance in many malignancies. The clinicopathological features of 140 primary canine osteosarcomas and their metastases were analysed, and the interrelations between them and an established grading system and its constituent parameters (mitotic index, necrosis, pleomorphism) were examined. Of these tumours, 35% were grade III (high-grade), 37% grade II and 28% grade I. Primary tumours that had metastasized were of significantly higher grade than non-metastatic osteosarcomas. Osteosarcomas belonging to the osteoblastic minimally productive subtype, but not chondroblastic or telangiectatic subtypes, differed from fibroblastic osteosarcomas in being associated with a significantly higher number of high-grade cases. Dogs younger than 4 years of age had osteosarcomas with higher grade, score and mitotic index than did older animals. Appendicular differed from axial tumours in having a higher mitotic index; distal differed from proximal tumours in being of higher grade; cranial tumours differed from tumours in most other sites in being of lower grade and lower mitotic index. Rib osteosarcomas showed a particularly high degree of necrosis. The mitotic index varied widely between tumour locations. Pleomorphism did not have prognostic merit when examined separately, as most osteosarcomas were highly pleomorphic.     

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.