Ki-67 Staining Index Research Articles

Stage II to IV Low-grade Serous Carcinoma of the Ovary Is Associated With a Poor Prognosis

Low-grade serous carcinoma (LGSC) of the ovary has only recently been recognized as a disease entity distinct from the more common high-grade serous carcinoma (HGSC). When confined to the ovary, LGSC is associated with a very favorable prognosis, and chemotherapy is typically not recommended. There is little available information on the prognosis of patients with LGSC with extraovarian spread, from population-based tumor registries where there has been full pathology review. Thirty-two cases of Stage II to IV ovarian LGSC were identified in the Cheryl Brown Ovarian Cancer Outcomes Unit (1984-2000). In 19 cases, blocks were available and immunostaining for p53, p16, Ki-67, WT1, and E-cadherin was performed. Expression of these markers was then compared with a series of >400 cases of HGSC from the outcomes unit. LGSCs presented at Stage II in 10/32 cases, Stage III in 21/32 cases, and Stage IV in 1/32 cases. On follow-up, most patients died of disease, with <30% survival at 10 years. Compared with HGSCs, the LGSCs were significantly less likely to express p16 at high levels, or to show abnormal p53 expression (P=0.049 and <0.0001, respectively). Ki-67 staining indices were lower in the LGSCs (P<0.0001). There were no significant differences between LGSCs and HGSCs with respect to expression of WT1 and E-cadherin (P=0.27 and 0.62, respectively). This population-based series of LGSC with extraovarian spread at presentation had an unfavorable prognosis, similar to that of HGSC. As previously reported, LGSC shows lower tumor proliferation and fewer p53 abnormalities than in HGSC.

Ki-67 Is an Independent Predictor of Metastasis and Cause-Specific Mortality for Prostate Cancer Patients Treated on Radiation Therapy Oncology Group (RTOG) 94-08

The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08. 468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria. In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P<.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation. High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

Clinicopathological features in the recurrence of oligodendroglioma and diffuse astrocytoma

To investigate whether grade II oligodendroglioma was transformed to glioblastoma or not, histopathological evaluation of recurrent oligodendrogliomal tumors (OG) and diffuse astrocytomas (DA) was performed. The OG group was composed of ten patients with OG, including seven oligodendrogliomas and three oligoastrocytomas. The DA group was composed of ten patients with DA, including eight fibrillary astrocytomas and two gemistocytic astrocytomas. The histopathological parameters of glioblastoma including nuclear atypia, multinucleated giant cells, glomeruloid tufts (GT) as a marker of microvascular proliferation, necrosis, and the Ki-67 staining index were investigated. Evaluation of these parameters was scored as follows: 0, none; 1, sporadic; 2, partial; 3, extensive. There were no cases of transformation to glioblastoma in the OG group. There were five cases of transformation to secondary glioblastoma in the DA group. In recurrent tumors, scores of GT and necrosis in the OG group were significantly lower than those in the DA group (p < 0.005). Nuclear atypia and high proliferative activity (Ki-67 index) were identified in recurrent tumors of the OG group. Our study suggested that the extent of GT and necrosis in recurrent OG was less than that in recurrent DA, and transformation to glioblastoma from oligodendroglial tumor was exceptional.

3′‐deoxy‐3′‐[18F]fluorothymidine positron emission tomography for response assessment in soft tissue sarcoma

This study sought to determine whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging allows assessment of tumor viability and proliferation in patients with soft tissue sarcomas who are treated with neoadjuvant therapy. Twenty patients with biopsy-proven, resectable, high-grade soft tissue sarcoma underwent [(18)F]FLT PET/CT imaging before and after neoadjuvant therapy. Histologic subtypes included sarcomas not otherwise specified (n = 5), malignant peripheral nerve sheath tumors (n = 3), gastrointestinal stromal tumors (n = 3), leiomyosarcomas (n = 3), angiosarcomas (n = 2), and others (n = 4). Changes in [(18)F]FLT peak standardized uptake value (SUVpeak) were correlated with percent necrosis in excised tissue, whereas posttreatment [(18)F]FLT tumor uptake was correlated with thymidine kinase 1 (TK1) expression and Ki-67 staining indices in excised tumor tissue. Tumor FLT SUVpeak averaged 7.1 ± 3.7 g/mL (range, 1.9-16.1 g/mL) at baseline and decreased significantly to 2.7 ± 1.6 g/mL (range, 0.8-6.0 g/mL) at follow-up (P < .001); however, marked reductions in SUV were not specific for histopathological response. The posttreatment SUVpeak did not correlate with TK1 (P = .27) or Ki-67 expression (P = .21). Marked reductions in [(18)F]FLT tumor uptake in response to neoadjuvant treatment were observed in most patients with sarcoma. However, these reductions were not specific for histopathologic response to neoadjuvant therapy. Furthermore, posttreatment [(18)F]FLT tumor uptake was unrelated to tumor proliferation by Ki-67 and TK1 staining. These results question the value of [(18)F]FLT PET imaging for treatment response assessments in patients with soft tissue sarcoma.

Surgical-Pathologic Risk Factors and Immunohistochemical Markers of Pelvic Lymph Node Metastasis in Stage IB1 Cervical Cancer

: This study aimed to identify the surgical-pathologic risk factors and immunohistochemical markers of pelvic lymph node metastasis in stage IB1 cervical cancer. : A retrospective review of patients with stage IB1 cervical cancer who underwent radical abdominal hysterectomy, lymph node dissection, and immunohistochemical staining for p53, bcl-2, and Ki-67 was performed. : A total of 29 patients with complete clinical data and pathology tissue blocks are the subjects of this study. Of these patients, 20 (69%) had squamous cell carcinoma, 8 (28%) had adenocarcinoma, and 1 (3%) adenosquamous carcinoma. The median tumor diameter as measured in the pathology laboratory was 2 cm. The median number of lymph nodes removed was 24. Four (14%) patients had positive lymph nodes. Lymphovascular invasion was noted in 10 (34%). None of the 19 patients without lymphovascular invasion had lymph node involvement. Of 29 patients, 2 (7%) had parametrial involvement. There was a statistically significant correlation between tumor diameter and depth of invasion (r = 0.43, p = .02), and between lymphovascular invasion and positive lymph nodes (r = 0.55, p = .0019). The Ki-67 immunostaining index was higher for patients with lymphovascular invasion and/or positive lymph nodes (p = .008 and p = .028, respectively). There was no association between p53 or bcl-2 expression and lymphovascular invasion or lymph node metastasis. : Lymph node metastasis (14 %) and parametrial involvement (7%) occurred only in patients with lymphovascular invasion and/or large tumor size. The Ki-67 staining index is associated with lymphovascular invasion and lymph node metastasis.

Atypical and ischemic features of embolized meningiomas

Preoperative embolization (POE) of meningiomas is widely used to facilitate surgical removal and to reduce intraoperative blood loss. The resulting necrosis and enhanced proliferation have been reported to affect subsequent histologic grading. However, there was little concern about ischemic features, for example small cells resembling atypical meningiomas, cytoplasmic vacuoles resembling clear cell meningioma, intercellular discohesion resembling rhabdoid meningioma, and perivascular cuffs resembling papillary meningioma. Therefore, the extent of these ischemic features was scored and Ki-67 staining indices were investigated in a POE group composed of 29 specimens of meningiomas treated with POE and compared with equivalent results for a non-POE group composed of 29 meningiomas that were not treated with POE. Small cells with high N/C ratios, cytoplasmic vacuoles, intercellular discohesion, and perivascular cuffs were significantly increased in the POE group (versus the non-POE group, p<0.05). There were no significant differences of the Ki-67 index between the POE group (2.2%) and the non-POE group (1.9%) (p=0.49). Our results suggest that small cell change resulting in necrosis may be followed by POE, and that clear cell-like, rhabdoid cell-like, or pseudopapillary pattern identified in meningiomas may also be induced by POE. Therefore, histological findings and determination of grading should be evaluated cautiously in cases of embolized meningiomas.

Temozolomide for corticotroph pituitary adenomas refractory to standard therapy

To highlight the potential of temozolomide (TMZ) to induce rapid tumor regression in patients with aggressive corticotroph adenomas (CA) that are refractory to surgery and radiation therapy and to review use of TMZ in other pituitary tumors. We present a case of a 56-year-old male with a 3 cm CA treated with transphenoidal surgery (TSS) and conventional radiotherapy in the same year. His hypercortisolemia recurred 11 years later with rapid tumor growth (to 4.2 × 2.5 cm) and he underwent a second TSS with good resection. The tumor recurred 6 months later with ophthalmoplegia. Over 16 months he underwent an additional three surgeries (two TSS, one craniotomy) and repeated conventional radiotherapy. Ki67 staining index on surgical specimens was 5-6%. Temozolomide is an oral alkylating agent approved for glioblastoma multiforme treatment that has only recently shown promise in treating some pituitary tumors. In this patient TMZ was started at 150 mg/m²/day, titrated to 200 mg/m²/day, taken 5 days per month. The only significant side effect was moderate nausea. After 10 weeks, the tumor showed a remarkable 60% regression with objective improvement in ophthalmoplegia. Treatment of aggressive CAs represents a therapeutic challenge and in some cases surgical debulking and radiotherapy are of limited success. Few reports of CAs responsive to TMZ have been reported in the literature. To our knowledge, this case represents the most rapid robust CA shrinkage response reported to date. Further randomized clinical trials of TMZ in the treatment of aggressive pituitary adenomas are warranted.

Analyses of Factors Influencing the Acute Effect of Octreotide in Growth Hormone-secreting Adenomas

Somatostatin analogues such as octreotide are used to treat active acromegalic patients by reducing serum growth hormone (GH) levels. However, the acute effect of octreotide on GH secretion differs among patients. To elucidate factors influencing the acute effect of octreotide, we collected data from 56 patients with somatotroph adenoma from two institutions. We analyzed the correlation of the following factors with the acute effect of octreotide: immunohistochemical staining of somatostatin receptor subtype 2A (SSTR 2A), presence of gsp mutation, proliferative potentials analyzed by Ki-67 staining index (SI). We found that the acute effect of octreotide significantly correlated with two factors: Ki-67 SI and the plasma membrane-dominant staining pattern of SSTR 2A. Monovariate analysis revealed a statistically significant inverse relation of Ki-67 SI with the reduction of GH by octreotide. We assessed the contribution of each factor on the acute effect of octreotide by multivariate analysis. Significant multiple regression was confirmed with p value of 0.003. Post-test revealed that the plasma membrane-dominant staining pattern of SSTR 2A was significantly related to the reduction of GH by octreotide. These results show that the acute effect of octreotide is positively related to SSTR 2A staining on the plasma membrane.

Effective Combined Medical Treatment With Octreotide Long Acting Release (Sandostatin LAR) and Cabergoline for an Extremely Rare Pituitary Somatotroph Adenoma Producing Growth Hormone-Releasing Hormone

Combined medical treatment with long acting octreotide and cabergoline is now used with active patients with acromegaly and can reduce serum growth hormone (GH) and insulin-like growth factor-1 levels. In this article, we analyzed again the molecular aspects of the previously reported rare GH-releasing hormone (GHRH)-producing somatotroph adenoma, and introduce the effects of the combined medical treatment using octreotide LAR and cabergoline for GHRH-producing somatotroph adenoma. The present GHRH-producing somatotroph adenoma had a high Ki-67 staining index, weak, and cytoplasmic-dominant immunostaining of somatostatin receptor 2A, and no gsp mutation. This adenoma was predicted to be resistant to the medical therapy using octreotide LAR. In this extremely rare GHRH-producing pituitary somatotroph adenoma, octreotide LAR alone cannot reduce random GH and insulin-like growth factor-1 levels sufficiently, but combined medical therapy with octreotide LAR and cabergoline can reduce them into the normal range. We show that combined medical treatment with octreotide LAR and cabergoline was effective for a somatotroph adenoma that had a high proliferative potential, weak and cytoplasmic-dominant immunostaining of somatostatin receptor 2A, and no gsp mutation, and has active GH production and secretion regulated by locally generated GHRH from adenoma cell.

High Cyclin E Staining Index in Blastemal, Stromal or Epithelial Cells Is Correlated with Tumor Aggressiveness in Patients with Nephroblastoma

PurposeIdentifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as a regulator of progression through the cell cycle and Ki-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies.Methodology/Principal FindingsA staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotherapy nephroblastoma including 42 nephroblastoma without metastasis and 12 with metastases. Median cyclin E and Ki-67 SI were 46% and 33% in blastemal cells, 30% and 10% in stromal cells, 37% and 29.5% in epithelial cells. The highest values were found for anaplastic nephroblastoma. A correlation between cyclin E and Ki-67 SI was found for the blastemal component and for the epithelial component. Univariate analysis showed prognostic significance for metastases with cyclin E SI in stromal cells, epithelial cells and blastemal cells (p = 0.03, p = 0.01 and p = 0.002, respectively) as well as with Ki-67 SI in blastema (p<10−4). The most striking data were that both cyclin E SI and blastemal Ki-67 SI discriminated between patients with metastases and patients without metastasis among intermediate-risk nephroblastoma.ConclusionsOur findings show that a high cyclin E SI in all components of nephroblastoma is correlated with tumor aggressiveness and metastases, and that assessment of its expression may have prognostic value in the categorization of nephroblastoma.

Ki67 staining index and neuroendocrine differentiation aggravate adverse prognostic parameters in prostate cancer and are characterized by negligible inter-observer variability

This study aims to clarify whether neuroendocrine differentiation (NED) and/or proliferation activity assessed by means of Ki67 staining index (Ki67SI) might aggravate other established adverse prognostic parameters commonly used for predicting outcome in surgically treated prostate cancer, and to assess inter-observer variability in assigning NED and Ki67 SI. A total of 528 patients surgically treated due to prostate cancer were evaluated in this study. Relevant data were retrospectively obtained by chart review. Immunostaining with antibodies directed against Chromogranin A and Ki67 was performed on archived surgical material, and was evaluated by two independent histopathologists blinded to the specimens. Surveying a median postsurgical follow-up of 46.4 months, postsurgical serum PSA-levels were regularly documented for identifying biochemical progress. Multivariate analysis was performed by means of the Cox regression hazards regression method to evaluate possible aggravations of established adverse prognostic parameters (nodal status, tumour stage, pretherapeutic PSA-level, and Gleason score) by NED and/or Ki67SI. Ki67 SI and NED were shown to significantly aggravate these established adverse prognostic parameters, and were found to be characterized by negligible inter-observer variability. Ki67 SI and NED should be advocated to be rendered by the histopathologist because both parameters can be immunohistochemically determined without much additional expense in time and cost involved. This concept is rewarded by an additional gain of prognostic accuracy in evaluating individual risk profile after surgery.

Neuroendocrine Differentiation in Primary Rectal Cancer: Immune Histology with Prognostic Impact?

Background: The aim of this study was to determine the incidenceand prognostic significance of neuroendocrine differentiation in primaryrectal cancer with special reference to ki-67 staining index.Methods: Formalin-fixed and paraffin-embedded tissue sections of94 rectal carcinomas were used for immunohistochemical analysisof chromogranin A (CgA), synatophysin (Syn) and neuron-specificenolase (NSE). Inclusion criteria were sporadic rectal adenocarcinomaresected curatively by total mesorectal excision, adjuvant radiochemotherapyin UICC stages II and III, and complete intrainstitutionalfollow-up. Results of immunohistochemistry were correlatedwith clinical and histopathologic data. End points of analysiswere tumor progression and 5-year survival. Statistics included univariateand multivariate analysis. Results: Of 94 rectal carcinomasstudied, 20% (19/94) were CgA-positive, 7% (7/94) were Syn-positive,and 3% (3/94) were NSE-positive. No expression of neuroendocrinemarkers was documented in 72% (68/94). There was no carcinomawhich expressed all three markers, and only 3% (3/94)showed a combination of at least two markers. Neither for Syn norfor NSE any significant association with clinical or histopathologicalvariables could be found. Expression of CgA significantly correlatedwith age and differentiation (p = 0.03). Within a mean follow-up of50 months, tumor progression occurred in 14 patients (15.4%):2 patients had local recurrences (isolated), 4 had local and distantrecurrence and 8 had metachronous distant metastases withoutlocal recurrence. Only UICC stage and preoperative CEA serumlevel were significantly associated with tumor progression, whereasthe neuroendocrine markers failed to show any correlation. Focusingsolely on distant recurrence, the incidence of metachronous distantmetastases was significantly associated with UICC stage, depthof invasion, preoperative CEA serum level, and CgA expression(23.5% in CgA-positive vs. 5.9% in CgA-negative tumors, p = 0.02).The neuroendocrine markers did not show any relation with survivalprognosis. Correlated to ki-67 expression, 89.5% (17/19) ofCgA-positive tumors showed a concurrent high ki-67 expression ofmore than 40% of cells (staining index > 0.4). Conclusions: The expressionof the neuroendocrine marker CgA seems to have a prognosticimpact in primary rectal cancer for the incidence ofmetachronous distant recurrence. It seems that the increased proliferation(assessed by ki-67 staining index) could play a role in curativelyresected rectal cancer.

Lymphoplasmacyte-Rich Meningioma With Atypical Invasive Nature-Case Report-

A 12-year-old boy presented with a lymphoplasmacyte-rich (LPR) meningioma in the posterior fossa. The tumor was subtotally removed. Histological examination showed the tumor had invaded the normal brain tissue despite its benign grade in the World Health Organization classification. The Ki-67 staining index using MIB-1 monoclonal antibody was relatively high. (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography revealed high uptake in the tumor. These findings indicate the atypical nature of LPR meningioma.

Huge Bilateral Pulmonary and Pleural Metastasis from Intracranial Meningioma: A Case Report and Review of the Literature

A case of recurrent meningioma with atypical features and extracranial metastases is reported. A 34-year-old female was operated in 1996, 2000, and 2002, and frontal parasagittal meningioma was extirpated. Histological diagnoses of all the resected tumors were meningotheliomatous meningioma, WHO Grade I. However, 2 years later, the tumor recurred in the frontal scalp and was removed again totally. Histological diagnosis was reported as an atypical meningioma; meningotheliomatous type; WHO Grade II. She received radiation therapy. But the tumor had metastasized to the lung and pleura. Transthoracic tru-cut biopsy was performed from large mass of the left lung. Cytopathology was consistent with malignant meningioma, metastasis from the patient's known intracranial meningioma. Ki-67 staining index at the primary and metastatic sites of the present cases were 7 and 5%, respectively. We reviewed and discussed the histopathological features and mechanisms of metastasizing meningioma.

Apoptosis in prostate cancer: Bax correlation with stage

Dysregulation of apoptosis may contribute to the process of prostate tumorigenesis by reducing the rate of cell death. Bcl-2 and bax are important molecules involved in the regulation of apoptosis. The aim of the present study is to examine apoptosis and related regulatory molecular markers in a group of Iranian patients with prostate cancer. Paraffin-embedded tissues from 50 patients of prostate carcinoma were examined for the expression of bcl-2 antiapoptotic and bax proapoptotic markers and also proliferation marker, Ki-67, by immunohistochemistry. Detection of apoptotic cells was performed using TUNEL method. Correlation between apoptotic index, proliferation index and bcl-2 and bax expression with stage, pathological grade and Gleason score was determined. Apoptosis was detected in 12% of prostate cancers. No correlation was observed between apoptosis and differentiation status of carcinoma. Bcl-2 expression was detected in 21 of samples. A significant correlation between bcl-2 expression and Ki-67 staining index (r = 0.349, P = 0.012) was observed. High bax protein expression was shown in our study. We found a significant correlation between bax expression and stage of carcinoma (r = 0.388, P = 0.031), but not with the apoptosis index, suggesting the presence of a non-functional bax protein or the role of other proapoptotic molecules. The patients in the present study showed a different pattern of apoptosis positivity compared to other reports. Bax expression may be a useful marker for prognosis of prostate cancer.

Does fetal gender affect cytotrophoblast cell activity in the human term placenta? Correlation with maternal hCG levels.

Pregnant women with female fetuses have higher maternal serum human chorionic gonadotropin (hCG) levels than pregnant women with male fetuses. Ki-67, a cell proliferation and activity marker, is confined mostly in the nuclei of villous cytotrophoblasts of the human placenta. In this study, we examined the effect of fetal gender on the cytotrophoblast cell activity in human term placenta, with special regard to maternal serum and cord blood hCG levels. Thirty-four uncomplicated, singleton, term pregnancies (17 male and 17 female fetuses) were recruited in the study. hCG was measured in maternal peripheral serum and umbilical cord blood. Placental samples were collected in each patient during the cesarean section. Cytotrophoblast cell activity was measured by using immunohistochemistry for Ki-67 antigen. Ki-67 staining index values of the cytotrophoblasts were compared between the female and male placentas. Maternal serum and cord blood hCG levels were higher in pregnant women with female fetuses than in those carrying male fetuses. There was no sex difference in Ki-67 immunostaining rates of the cytotrophoblast cells. There was no correlation between maternal serum and cord blood hCG levels and Ki-67 staining index values of the cytotrophoblast cells. The difference in maternal serum and cord blood hCG levels in correlation with the fetal gender is not associated with cytotrophoblast cell activity in the human term placenta. The gender of the fetus does not seem to affect the regulation of cytotrophoblast cell proliferation.

Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: an analysis of patients in radiation therapy oncology group protocol 86-10.

Proliferative activity defined by Ki-67 staining index (SI) has been correlated with progression and prognosis in a number of malignant tumors including prostate cancer. However, few studies have examined Ki-67 SI in pretreatment diagnostic material from patients treated with definitive radiotherapy. In a prior study, we found that a Ki-67 SI of >3.5% was associated with poorer patient outcome. The goals of this analysis were to validate the prognostic value of Ki-67 SI and this cut point. Of 456 assessable patients in Radiation Therapy Oncology Group Protocol 86-10, diagnostic material from 108 patients was available for Ki-67 analysis using MIB-1 antibody. Sixty patients were treated with external beam radiotherapy (EBRT) alone, and 48 patients were treated with short-term androgen deprivation + EBRT. Median follow-up was 9 years for those living. The relationship of Ki-67 with distant metastasis (DM), disease-specific survival (DSS), and overall survival (OS) was examined. The median Ki-67 SI was 7.1% (range, 0.2-45.5%). The 7.1% cut point was associated with DM and DSS; however, the 3.5% cut point was as strong a determinant and was the focus of this analysis. In Cox proportional hazards regression, Ki-67 SI was independently associated with DM and DSS. When the Ki-67 SI was </=3.5% and >3.5%, the 5-year risk of DM was 13.5% and 50.8% (P = 0.0005), respectively, and the 5-year risk of DSS was 97.3% and 67.7% (P = 0.0039), respectively. No association of Ki-67 SI with OS was observed. Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT.

Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92-02.

The Ki-67 staining index (Ki67-SI) has been associated with prostate cancer patient outcome; however, few studies have involved radiotherapy (RT) -treated patients. The association of Ki67-SI to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAD) + RT or long-term androgen deprivation (LTAD) + RT. There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-SI analysis. Median follow-up was 96.3 months. Ki67-SI cut points of 3.5% and 7.1% were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-SI was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P =.08), BF (P =.0445), DM (P <.0001), CSD (P <.0001), and OD (P =.0094). When categoric variables were used in MVAs, the 3.5% Ki67-SI cut point was not significant. The 7.1% cut point was related to BF (P =.09), DM (P =.0008), and CSD (P =.017). Ki67-SI was the most significant correlate of DM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAD + RT that did not require LTAD. Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.

The combination of mitotic and Ki-67 indices as a useful method for predicting short-term recurrence of meningiomas

Background The most relevant factor in the progression-free survival (PFS) of patients with meningiomas is the malignant grade. However, using only the current World Health Organization (WHO) definition that does not consider precise quantitative indicators, an unequivocal diagnosis of the malignant grade is difficult. In our retrospective study of the PFS of meningioma patients, we focused on mitoses and the Ki-67 staining index of tumor specimens obtained at the initial surgery. Methods and results A total of 349 patients with intracranial meningioma, operated between 1978 and 2000, were followed for a mean of 7 years. According to the mitotic index (MI), we classified them into 3 groups. In Group A ( n = 326), slide-mounted tumor samples exhibited no mitoses; in Group B ( n = 15) there were fewer than 4 mitoses, and in Group C ( n = 8) 4 or more mitoses were seen per 10 high-power fields (HPF). The estimated 5-year PFS rates in Groups A, B, and C were 93%, 10%, and 13% respectively. The mean PFS for Group A was 148 months; in Groups B and C the median PFS was 43 and 16 months, respectively. A Ki-67 staining index (SI) of less than 1% corresponded with no mitosis, while an SI exceeding 5% was indicative of the presence of mitoses. Conclusion In meningioma patients, no mitoses and/or a Ki-67 SI <1% signals a favorable outcome. An SI >5% or the presence of mitoses, even fewer than 4 in 10 HPF, is suggestive of a short PFS irrespective of other pathologic features. We suggest that in combination, assay of the Ki-67 SI and the MI represents a reliable, quantitative tool for predicting PFS in meningioma patients.

E, N-Cadherins and beta-Catenin Expression in Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor

Cadherins are cell-surface glycoproteins that mediate Ca2+-dependent, homophilic cell-cell adhesion. The classical cadherins, E- and N-cadherins, bind to beta-catenin, the lining protein. Dysfunctional expression of these factors seems to be related to tumor invasion and metastasis. This study examined the relationship between changes in E- and N-cadherins, and catenin expression, and biological behavior in medulloblastomas and atypical teratoid/rhabdoid tumors. Specimens of 13 medulloblastomas and two atypical teratoma/rhabdoid tumors were collected and stained immunohistochemically to detect E- and N-cadherins, and beta-catenin. None of the medulloblastomas were immunoreactive for E-cadherin, but both atypical teratoma/rhabdoid tumors were immunoreactive for E-cadherin at the cell-cell borders where epithelial differentiation occurred. In contrast, N-cadherin and beta-catenin were present at the cell-cell borders in 12 of the 13 medulloblastomas and both atypical teratoma/rhabdoid tumors. Nuclear beta-catenin staining was not present in the medulloblastomas or atypical teratoma/rhabdoid tumors. There was no significant difference in the Ki-67 staining index between patients with medulloblastomas showing high and low immunoreactivity for N-cadherin and beta-catenin. Moreover, immunoreactivity for N-cadherin and beta-catenin increased with dissemination in the medulloblastomas. Low immunoreactivity in medulloblastomas tended to be associated with a better prognosis. These results suggest that expression of E-cadherin is useful for the differential diagnosis of atypical teratoma/rhabdoid tumor and medulloblastoma, and the expression of N-cadherin or beta-catenin may be related to the biological behavior of medulloblastomas.