Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67.

The growth fractions of 160 mammary carcinomas and 30 benign mammary lesions were determined in situ by immunostaining with the monoclonal antibody Ki-67. Benign lesions had a mean value of 3% Ki-67 positive cells, whereas the mean value of mammary carcinomas was 16.6%. A comparison of the mean values of Ki-67 positive cells with the histological grade of the tumours showed a correlation between these two variables--that is, histological grade 1 showed 9%, grade 2 16%, and grade 3 26% proliferating cells. Considering the individual Ki-67 values in the different histological grades, it was evident that there was considerable scatter in the number of proliferating cells, so that the proliferation rates of grades 1, 2, and 3 overlapped each other. This indicates a dissociation between histological grade of malignancy and size of the growth fraction in most breast cancers. Follow up studies are needed to establish which of the two variables--that is, morphological degree of malignancy, or the proportion of Ki-67 positive cells--correlates better with response to treatment and survival in individual cases.     

A comparison between Ki-67 antibody reactivity and other pathological variables in breast carcinoma.

Methods of assessing tumor proliferation rates include mitosis counting, flow cytometry and thymidine labelling. While the former is inaccurate and poorly reproducible, the latter methods are time consuming and expensive to perform. Ki-67 is a monoclonal mouse antibody which has been shown to react with a nuclear antigen in proliferating cells. Frozen sections from 75 specimens of breast carcinoma were immunostained with this antibody using an immunoperoxidase technique. The percentage of tumor cells stained, the Ki-67 score, was then compared with a number of pathological and clinical variables in the patients concerned. A positive correlation was seen between the Ki-67 score and mitotic rate (r = 0.71); and a negative correlation was seen between Ki-67 score and estrogen receptor status (r = -0.4). Ki-67 immunostaining may represent a cheap and reproducible method of assessing proliferation rates of breast carcinomas which is applicable in routine laboratories. Further prospective studies are being undertaken to assess its contribution to prognosis.     

A cautionary note regarding the application of Ki-67 antibodies to paraffin-embedded breast cancers

Immunocytochemical studies examining the Ki-67 proliferation marker in paraffin-embedded material have recently been made possible by the availability of several antibodies, notably MIB-1, which are readily applicable to microwaved sections. Using breast cancer material, the present study examines correlations shown by these new paraffin assays and also by PCNA (proliferating cell nuclear antigen), an existing marker of proliferation, with the established Ki-67 cryosection assay. Paraffin sections were microwaved prior to incubation with Ki-67 or MIB-1 antibodies. Signal detection was carried out with a biotinylated secondary antibody, peroxidase-conjugated streptavidin, and DAB/H₂O₂ chromogen. The results suggest that caution is required when studying proliferation in paraffin-embedded breast cancers by immunostaining using Ki-67 antibodies. Nuclear staining in wax sections (Ki-Par, MIB-1, PCNA) greatly exceeded that in cryosections (Ki-Froz) and thus correlations were notably absent between Ki-Par or PCNA immunostaining and the routine Ki-Froz assay. Immunostaining with MIB-1 or PCNA may, however, be useful to assess proliferation if cut-offs are applied to eliminate weak immunostaining associated with wax sections. Thus, an approximately linear relationship was seen between MIB-1/Ki-Froz, which was improved if only moderately or moderately/strongly MIB-1-positive cells were scored. Similarly, a significant correlation was also revealed between PCNA/Ki-Froz if such a cut-off was applied.     

Ki-67 reactivity in breast carcinoma analyzed by a computer-assisted image system: preliminary results.

The proliferative index of 63 breast carcinomas was measured on Ki-67 immunostained frozen tissue sections with a computer-assisted image analysis system. The mean proliferative index in estrogen-positive breast carcinomas was lower than in estrogen-negative carcinomas. An inverse relationship between proliferative index and short-term disease-free survival was noted.     

Role of radiotherapy in the management of primary carcinoma of the fallopian tube

Primary fallopian tube carcinoma is a rare neoplasm. It may be postulated that postoperative loco-regional radiotherapy is a valuable adjunctive in the overall management of the tubal carcinoma. However, we can't advocate the efficacy of this approach authentically due to a very small number of cases. A prospective controlled and randomized trial with larger patient number may yield some definite conclusions regarding it's optimal management.     

Adenocarcinoma of the fallopian tube

Summary A case of fallopian tube adenocarcinoma was studied by light and transmission electron microscopy. The neoplastic cells contained abundant mitochondria, moderate to large amounts of rough endoplasmic reticulum (RER) arranged in parallel arrays and often containing amorphous material, annulate lamellae, possible secretory vesicles, and glycogen. The presence of stacked RER and annulate lamellae together is unusual in papillary serous cystadenocarcinoma of the ovary, and has not been described in Fallopian tube adenocarcinoma. Golgi complexes were are. Small acini with projecting microvilli as well as junctional complexes were present, but cilia were not found. The electron microscopic findings suggest secretory activity, and are remarkably similar to those found in papillary serous cystadenocarcinomas of the ovary. The findings also support the hypothesis that ovarian serous tumors and adenocarcinomas of the Fallopian tube are derived from coelomic epithelium.     

Polyp of the fallopian tube

The case of a 34-year-old woman who had a radical hysterectomy for stage 1 b squamous cell carcinoma of the cervix and in whom an epithelial polyp was identified in the left fallopian tube is presented. The case is unusual in that the polyp developed in the absence of any evidence of tubal damage as demonstrated by a history of endometriosis or tubal sterilisation.     

Comparison of Ki-67 equivalent antibodies

AIMS: To compare commercially available Ki-67 equivalent antibodies with regard to qualitative and quantitative immunohistochemical staining characteristics. METHODS: The following antibodies were used: monoclonal MIB-1 (Immunotech), monoclonal MM1 (Novocastra), polyclonal NCL-Ki-67p (Novocastra), and polyclonal Rah Ki-67 (Dako). All immunostainings were evaluated in squamous epithelium from formalin fixed and paraffin wax embedded pharyngeal tonsils. Labelling indices (LIs) were recorded twice to test their reproducibility. RESULTS: By application of all four antibodies the nuclear staining could be either diffuse, granular, or a combination of both (classified as granular in this study). The diffuse pattern generally showed a strong or moderate staining intensity, whereas the granular pattern displayed a continuum from strong to very weak, making it difficult to discriminate between positive and negative nuclei. The diffuse staining pattern was seen in approximately 59% of the nuclei with the MIB-1 antibody and in 35-45% when the other antibodies were used. The following mean LIs were recorded: MIB-1, 31%; NCL-Ki-67p, 21%; Rah Ki-67, 17%; and MM1, 14%. The reproducibility was excellent for all four antibodies, with the mean of differences between the two runs of counts ranging from 1.1% to 1.5%. CONCLUSIONS: The four tested Ki-67 equivalent antibodies revealed differences in qualitative and quantitative staining characteristics, which resulted in considerable variations in registered LIs. The MIB-1 antibody appears to have a higher sensitivity for detecting the Ki-67 antigen than the other three tested antibodies. These differences are important to consider when proliferative activity is determined by the Ki-67 LI.     

肺癌中P63与P53、E-cadherin、Ki-67表达的比较

目的　比较 p6 3及 p5 3、E cadherin(E cad)、Ki 6 7在肺癌中的表达 ,以了解在不同组织类型肺癌发生发展过程中 ,p6 3与抑癌基因 (p5 3)突变、上皮分化标志基因 (E cad)失活及细胞增殖标志基因 (Ki 6 7)激活有无相关性。方法　采用免疫组化S P法分别检测 6 1例原发性肺癌中 p6 3、p5 3、E cad和Ki 6 7的表达情况。 结果　p6 3在肺鳞癌中阳性率为 10 0 0 % ,而在其他组织类型肺癌中 p6 3基本不表达 ,差异有显著性 (P <0 0 5 ) ;在不同分化程度的肺鳞癌中 p6 3、p5 3的表达差异有显著性 (P<0 0 5 ) ,E cad、Ki 6 7的表达差异无显著性 (P >0 0 5 ) ;E cad的表达在小细胞肺癌与肺鳞癌和肺腺癌之间差异有显著性 (P <0 0 5 ) ;Ki 6 7的表达在各种组织类型肺癌之间差异有显著性 (P <0 0 5 ) ;在不同分化程度鳞癌中 p6 3与E cad的表达呈负相关(P <0 0 5 )。结论　p6 3可作为鳞状上皮源性肿瘤标记物 ,是判断鳞状细胞癌的增殖和分化有意义的指标 ,并可作为鉴别分化差的鳞癌和腺癌、小细胞癌的指标。     

Ki-67 expression in primary breast carcinomas and their axillary lymph node metastases: clinical implications

Proliferative activity of tumour cells assessed by immunohistochemical Ki-67 expression is one of several prognostic indicators in breast cancer. The major objective of this study was to investigate the prognostic impact of Ki-67 proliferative activity in the axillary lymph node metastases and in the matched primary breast carcinoma from 194 patients. There was a statistically significant up-regulation of Ki-67 protein in the metastatic deposit compared to where the primary tumour was found (p = 0.001). A low Ki-67 index in both the primary and the metastatic tumours was a favorable prognostic factor. A high index in both primary and metastatic lesion and an up-regulation from a low index in the primary tumour to a high index in the metastatic deposit represented an unfavorable prognostic factor. Multivariate analysis showed that Ki-67 expression in the metastases was a superior independent prognostic factor of clinical outcomes compared to that in the primary tumours. Ki-67 expression in ≥10% of carcinoma cells in the primary tumours and ≥15% in the nodal metastases seems to be optimal cut-off levels. Ki-67 is of value as an independent prognostic factor in breast cancer.     

Ki-67 and biological behaviour in meningeal haemangiopericytomas

The biological behaviour of meningeal haemangiopericytomas was retrospectively studied using immunohistochemical staining with MIB1, a monoclonal antibody against the Ki-67 antigen, a nuclear protein related to cell proliferation. Paraffin-embedded material from 62 tumours from 40 patients were investigated. The proliferating compartment of the tumours was estimated by evaluating the MIB1 staining index, i.e. the percentage of MIB1 positive nuclei in at least 1000 counted tumour cells in representative areas. The staining index ranged from 1.24% to 39.01%. Statistical analysis revealed no significant correlation between the staining index and recurrence-free survival (χ² = 0.3922, P  = 0.5311). Long-term observation (>100 months), however, revealed a tendency to longer survival in the group with a staining index less than 5%. According to our results, the MIB1 staining index does not contribute to the accuracy of predicting the clinical outcome of meningeal haemangiopericytomas.     

Extraskeletal chondroma of the fallopian tube

Extraskeletal chondroma can occur in the hands, feet, head and neck. This tumor usually presents as a small solitary nodule. The histogenesis of the tumor is controversial, but some have suggested a metaplastic origin. Chondroma of the fallopian tube is very rare. There is only one report in English literature. The origin of this tumor can be subcoelomic mesenchyme of the tubal serosa or mesenchyme of the myosalpinx. We describe a case of chondroma arising from the serosal surface of the fallopian tube with a review of literature. A 30-yr-old woman visited hospital due to left adnexal mass. On operating finding, 2 x 3 cm sized nodular mass was noted on the left tubal serosal area. The excised mass showed multilobulated appearance covered with thin fibrous membrane. The cut surface was solid, grayish yellow, and myxoid with a focal gelatinous area. The microscopic finding showed islands and elongated lobules of mature benign cartilage without cytologic atypia.     

Herpetic salpingitis and fallopian tube prolapse

AIM: We describe the unusual association of fallopian tubal prolapse and herpetic infection, an occurrence not previously reported to our knowledge. METHODS AND RESULTS: A 37-year-old woman presented with a small polypoid mass of the vaginal vault, 3 months after abdominal hysterectomy and abdominoplasty. The vaginal mass proved to be the fimbriated end of a fallopian tube, herniated into the vagina. Reintervention 3 months later with resection of a small vaginal 'polyp' revealed a residual portion of fallopian tube, with superimposed herpes simplex virus (HSV) infection and marked cytological atypia of surface epithelial cells. HSV-2 immunostaining of viral nuclear inclusions and of atypical cells confirmed the herpetic nature of the infection. CONCLUSION: Involvement of the genito-urinary tract by HSV may occur via an ascending infection from the cervix, but the fallopian tube, deeply located in the pelvis, is generally spared from herpetic infection. In the setting of fallopian tubal prolapse, direct exposure of the herniated fallopian tube to various pathogens in the vagina provides an unique clinical model for salpingitis. In herpetic tubal infections, special attention must be paid to cytological atypia of probable viral cytopathogenic origin, to avoid a misdiagnosis of malignancy.