Median MIB-1 Index Research Articles

The extended, transnasal, transsphenoidal approach for anterior skull base meningioma: considerations in patient selection.

In this study, we set out to define our institutional criteria for patient eligibility for transsphenoidal resection of parasellar meningiomas, and to report our experience with extended transnasal approaches for these lesions. We aimed to discuss the important considerations of patient selection and risk stratification to optimize outcomes for patients with these difficult lesions, and also include considerations that should be reviewed during surgical approach selection. Medical records from Brigham and Women's Hospital were retrospectively reviewed for all patients who underwent transsphenoidal surgery for pituitary disease with the senior author from April 2008 to March 2017 (938 procedures). Patients undergoing surgery for anterior skull base meningioma were identified and patient data were collected. Seven patients (four women, three men) underwent transsphenoidal resection (five endoscopic, one microscopic, and one hybrid endoscopic/microscopic) of pathologically-confirmed anterior skull base meningiomas during the study period. Five patients presented with visual field deficits, three presented with headache, two presented with hypopituitarism, and one woman presented with infertility. The median maximum tumor diameter was 1.7cm (range 1.4-4.2cm). Six patients underwent subtotal resection, and one underwent gross total resection. The median MIB-1 index was 2.3 (range 1.0-7.6). Complications included two readmissions (one on POD11 for small bowel obstruction, one on POD48 for epistaxis), and the development of new onset thyroid deficiency and transient diabetes insipidus in one patient. Two patients had reoperations by craniotomy for tumor recurrence after 5 and 6 years, respectively. Although more commonly treated transcranially, anterior skull base meningiomas are sometimes amenable to resection transphenoidally. Patient selection is critical, and multiple factors, including tumor size, consistency, and location, patient and surgeon preference, and presenting symptoms each affect the optimum surgical approach. We have developed criteria for patient selection so that transsphenoidal surgery can be used to resect or debulk anterior skull base meningiomas safely and with favorable outcomes.

ATCT-17IMPACT OF ADVERSE RADIOLOGICAL AND HISTOPATHOLOGIC CHARACTERISTICS ON OUTCOME OF AGGRESSIVE ADULT LOW GRADE GLIOMAS TREATED UNIFORMLY WITH RADIOTHERAPY AND CONCURRENT AND ADJUVANT TEMOZOLOMIDE: AN ANALYSIS OF 47 PATIENTS

BACKGROUND: We investigate the impact of adverse radiology and histopathologic characteristics in adult low-grade gliomas (LGG) treated uniformly with post-operative radiotherapy with concurrent and adjuvant Temozolomide (TMZ). We also compare outcomes with published RTOG-9802 and RTOG-0424 trials data. METHODS: Between February 2009 to March 2014, 47 patients with supratentorial aggressive LGG selected meticulously based on predefined high-risk features on pre-operative MRI and histomorphology [nuclear pleomorphism suggesting atypical histology, high cellularity/mitosis, high Mib-1 index, and/or radiological features like definite gadolinium enhancement or considerable heterogeneity on T2 fluid-attenuated inversion recovery (FLAIR)]) were treated with post-operative RT with concurrent (75mg/m2) and adjuvant TMZ (150-200 mg/m2) for 6-12 cycles. All patients had either subtotal resection/biopsy/or had 3 or more Pignatti's high risk factors. RESULTS: Median age of the cohort was 35 years. Histologies included astrocytoma in 17 patients, oligodendrogliomas in 11 patients and mixed in remaining. Median RT dose was 55.8 Gy, median TMZ cycles were 6. The median Mib-1 index was 4 (range 2-15%). P53 mutation was present in 19/25 tested samples. 1p19q co-deletion was found in 11/22 tested samples. IDH 1 was mutated in 5/9 cases tested. At a mean follow up of 31 months, the 3 year and 5 year OS was 86% and 73% respectively, while PFS was 82% and 61% respectively. For 31 patients having 3 or more Pignatti's high risk factors, 3 year OS and PFS were 85% and 73% respectively. Five patients had clinic-radiological progression, while two patients had transformation to glioblastoma. No grade III/beyond toxicity was reported. CONCLUSION: Our experience of employing TMZ in concurrent and adjuvant setting along with focal irradiation in aggressive adult LGG, based on adverse radiological and histopathologic factors, even without all molecular markers is encouraging. Future work will include late follow-up data and impact of molecular markers in this cohort.

AT-42 * FACTORS ASSOCIATED WITH MALIGNANT TRANSFORMATION OF LOW-GRADE GLIOMA

BACKGROUND: There is no standard therapeutic regimen for low-grade glioma (LGG). We have suggested extent of resection (EOR) was strongly associated with prognosis of LGG. About half of LGG eventually show malignant transformation (MT), MT is an important factor in determining prognosis of LGG. Therefore, it is important to definite factors associated with MT. In this study, we investigated correlation between MT and genetic profile and adjuvant therapy in LGG. METHOD: 151 patients (Male: Female = 80:71) with LGG treated in our institute from 2000 to 2010 were retrospectively analyzed. Median follow-up period was 41months, follow-up ratio was 96°, and the average age was 39.1 year-old (15-65). Diffuse astrocytoma (DA) accounted 47 patients (31°), oligodendroglioma (O) was 55 patients (37°), oligoastrocytoma (OA) was 44 patients (29°). The median Mib-1 index was 4.8°. IDH1 mutation and co-deletion of 1p19q locus were analyzed by immunohistochemistry and FISH method, respectively. RESULT: The average and median EOR of T2 high area was 85° and 95°, respectively. ACNU based chemotherapy was performed in 35 patients and radiotherapy in 48 patients. IDH1 mutation and 1p19q co-deletion were 75° and 57%, respectively. 48 patients out of 151 recurred and 29 patients were MT. Patients without IDH1 mutation (P = 0.025) or 1p19q deletion (P = 0.001) showed significant higher rate of MT. In analysis of all patients, EOR strongly correlated with MT (P = 0.0002). EOR correlated with MT in DA (P = 0.0003) but not in oligodendroglial subtypes (P = 0.7). In IDH1 mutant group, chemotherapy reduced MT (P = 0.004), however, in IDH1 wild-type group, both radiotherapy (P = 0.004) and chemotherapy (P = 0.006) brought higher incidence of MT. CONCLUSION: EOR significantly prevented MT in DA. It was suggested that IDH1 was a predictive factor for MT following radiotherapy and chemotherapy in LGG. Extensive resection is required for IDH1 wild type DA.

MIB-1 Labeling Index As a Prognostic Factor in Patients with Follicular Lymphoma Treated with R-CHOP Therapy

AbstractAbstract 1561Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma (NHL), with a highly variable natural history, ranging from an indolent disease to a rapidly progressive disease such as transformation to aggressive NHL. The MIB-1 labeling index, based on the Ki67 immunostaining, is widely used for evaluating the proliferation of tumor cells.We retrospectively evaluated the prognostic impact of the MIB-1 labeling index at diagnosis in patients with FL treated with rituximab plus cyclophosphamide, doxorubicine, vincristine, and prednisolone (R-CHOP) alone. Ninety-eight consecutive FL patients (48 men and 50 women; median age, 57 years [range, 34–85 years]) were enrolled in one of the 7 participating hospitals between 2001 and 2009. Since 2001, the Yokohama City University Hematology Group in Japan has uniformly treated FL patients with curative intent, except for those in stage 1 disease, with 6 cycles of standard R-CHOP therapy for 21 days. Patients who had partial response (PR) after the 4 initial cycles were administered a total of 8 R-CHOP cycles, whereas patients who did not achieve PR after the 4 initial R-CHOP cycles or those who exhibited disease progression at any given time received salvage therapy. Patients who had a bulky mass defined as any mass exceeding 10 cm in diameter in a horizontal plane or a mediastinal mass with a maximum diameter exceeding one-third of the maximum chest diameter, received additional irradiation following CR with 6–8 cycles of R-CHOP. Patients who required a dose reduction of more than 20% were excluded from this study. The pathological diagnosis and MIB-1 labeling index were reviewed by 3 hematological pathologists (S. S., N. Ts., and K.T.).The WHO pathological grading in patients was as follows: grade1 in 63 patients, grade 2 in 21 patients, grade 3a in 12 patients, and grade 3b in 2 patients. The median MIB-1 index was 12.9% (range, 0.8%-79.9%). The median observation period for living patients was 59 months. The estimated 5-years progression-free survival (PFS) and 5-years overall survival (OS) rates were 48% and 84%, respectively. Patients with a MIB-1 index above 10% (n = 60) showed inferior survival curves compared with patients with a MIB-1 index below 10% (n = 38) in PFS (5-year PFS of 35% versus 67%, P = 0.02; Figure 1) and OS (5-year OS of 77% versus 94%, P = 0.009), respectively. Pathological grading was not correlated with PFS and OS. The following variables were assessed for their impact on PFS: (1) gender, (2) age > 60 years, (3) elevated serum lactate dehydrogenase level, (4) advanced clinical stage, (5) pathological grade, and (6) a MIB-1 labeling index above 10%. A MIB-1 labeling index above 10% was independently associated with poor PFS (P = 0.01, RR = 2.6), as well as advanced clinical stage (P = 0.004, RR = 2.7).A MIB-1 labeling index of above 10% is a useful prognostic factor in FL treated by R-CHOP. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Prediction of Treatment Outcomes in Patients with Chest Wall Sarcoma: Evaluation with PET/CT

The aim of this study was to investigate the prognostic implications of (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography in patients with chest wall sarcoma. Positron emission tomography/computed tomography scans of 42 patients (mean age: 46 years) with chest wall sarcomas were analyzed. Pathologic confirmation was obtained by surgical specimens in all patients. Tumor grade assessed by Ki-67 (MIB-1) immunohistochemical analysis and expression of glucose transporter protein 1 were compared with a maximum standardized uptake value. Univariate and multivariate analyses were conducted for estimates of overall and event-free survivals. The median maximum standardized uptake value of the tumor was 10.2 and the median MIB-1 index of the tumor was 32.5%. Glucose transporter protein 1 expression was found in 29 patients (69%). Univariate analyses revealed that surgery, chemotherapy, MIB-1 labeling index (cut-off 32.5%), MIB-1 grade, glucose transporter protein 1 expression and maximum standardized uptake value were possible predictors for overall and event-free survival. Multivariate analysis revealed that surgery (hazard ratio, 4.852; P = 0.017), maximum standardized uptake value (hazard ratio, 3.077; P = 0.037) and MIB-1 labeling index (hazard ratio, 6.549; P = 0.003) were independent predictors of event-free survival. In addition, surgery (hazard ratio, 4.092; P = 0.021) and maximum standardized uptake value (hazard ratio, 2.968; P = 0.027) were independent predictors of overall survival. (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography allows the prediction of prognosis after treatment in patients with chest wall sarcoma and may be useful in selecting high-risk patients for more risk-adapted treatments.

Risk Factors for Regrowth of Intracranial Meningiomas after Gamma Knife Radiosurgery: Importance of the Histopathological Grade and MIB-1 Index

The influence of histopathological grade and MIB-1 index of intracranial meningioma on the results of its radiosurgical management is not clear. The objective of the present retrospective study was to make an evaluation of these factors along with an analysis of other variables associated with progression-free survival after gamma knife radiosurgery (GKR). Thirty-four intracranial meningiomas with known detailed histopathological diagnosis were analyzed. Tumors of WHO histopathological grades I, II, and III were diagnosed in 24, 3, and 7 cases, respectively. The median MIB-1 index was 1.3% (range: 0-31.9%). In 14 cases the MIB-1 index was 3.0% and more. In 26 cases the treatment was done at the time of tumor recurrence. Median volume of the neoplasm at the time of GKR was 4.1 mL (range: 0.4-43.1 mL). Median marginal dose was 12 Gy (range: 8-19 Gy). Median length of follow-up constituted 63 months (range: 19-132 months). Actuarial progression-free survival at 1, 3, 5, and 10 years constituted 100, 94, 83, and 58%, respectively. Histopathological grade II or III (p<0.0001), MIB-1 index 3% and more (p=0.0004), and non-skull base location (p=0.0026) of the tumor showed negative associations with progression-free survival in multivariate analyses. Actuarial progression-free survival at 5 years after GKR for benign and non-benign meningiomas constituted 100 and 45%, respectively (p<0.0001). Radiosurgery is a highly effective management option for benign intracranial meningiomas, but growth control of non-benign ones is significantly worse. It requires close neuroradiological follow-up and necessitates the search for modified treatment strategies.

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

Proliferating fibroblasts at the invading tumour edge of colorectal adenocarcinomas are associated with endogenous markers of hypoxia, acidity, and oxidative stress

Background: Stroma frequently forms at sites of active tumour invasion, and may be important for tumour growth and progression. The term “stromatogenesis” is used to describe this unique process that...

MIB-1 index in thyroid tumors: a predictor of the clinical course in papillary thyroid carcinoma.

MIB-1 is useful in evaluating proliferative activity and in predicting the aggressiveness in a variety of tumors. To investigate if MIB-1 immunoreactivity can add prognostic information to conventional prognostic variables in papillary thyroid carcinoma (PTC), 30 PTCs were evaluated using the MIB-1 antibody. For comparison, 10 follicular thyroid carcinomas (FTC), 8 anaplastic thyroid carcinomas (ATC), and 96 follicular thyroid adenomas (FTA) were similarly analyzed. The median MIB-1 index was 0.5% in FTA, 1.9% in PTC, 2.7% in FTC, and 16.2% in ATC. The 13 tumors from patients classified as having aggressive PTC (defined as dead from disease, persisting disease, or the occurrence of distant metastases) had significantly higher MIB-1 index (median, 5.4%) than the 17 patients with nonaggressive disease (median, 1.1%). MIB-1 index 1.85% or more was found to be an independently significant risk factor for a less favorable clinical course in PTC. Because of overlap of single values the utility of MIB-1 index as a clinical test is somewhat limited. Still, at levels where no overlap occurs (MIB-1 index 2 3.2% or ' 0.5%) the index seems to add information to the established prognostic parameters. MIB-1 index should therefore be considered in routine histopathology of PTC.

Apparent lack of prognostic value of MIB-1 index in anal carcinomas treated by radiotherapy

This study was conducted to investigate the influence of Mib-1 index on outcome in 55 patients with T1-4 anal carcinomas treated radically by radiotherapy (RT) alone (24) or by concomitant chemo-radiotherapy (31). Median follow-up for surviving patients was 94 months (range 17-179 months). Tissue materials were obtained from pretreatment biopsies. A modified immunoperoxidase technique consisting of microwave heating of routinely processed material was employed using the Mib-1 antibody (Immunotech, 1:50). The median Mib-1 index for all patients was 53% (range 18-96%). Subgroups of patients with high vs low Mib-1 indices (separated by the median value) had statistically similar outcomes regarding 5-year overall survival (64% vs 65% P = 0.7), locoregional control (77% vs 69%, P = 0.5) and disease-free survival (73% vs 66%, P = 0.5). Moreover, no significant association was found between mean Mib-1 indices and various clinicopathological parameters studied (age, sex, circumferential tumour extent, T-stage, N-stage and histological type). In conclusion, Mib-1 index failed to predict the outcome of patients with anal carcinomas treated conservatively by radiotherapy with or without chemotherapy. It is noteworthy that the median Mib-1 index observed in anal carcinomas in this study was among the highest yet reported for cancers of epithelial origin.

MIB-1 and involucrin expression in laryngeal squamous carcinoma: the relationship to host and tumour factors and survival.

MIB-1 is an antibody which attaches to the Ki67 antigen expressed by proliferating cells. MIB-1 immunoreactivity may be used to quantify the proliferative component of a tumour. Involucrin is a protein expressed by mature keratinocytes and may be used as a marker of differentiation. The present paper studies the expression of these two markers in a group of patients with squamous carcinoma of the larynx. Tumour cell kinetics were studied in 49 patients with squamous cell carcinoma of the larynx using antibodies to "Ki67' and involucrin. The median potential follow-up for the group was 8.1 years with a minimum follow-up of 5 years. The median MIB-1 index was 32%. The median involucrin index was 56%. Fifteen patients had no or only slight involucrin staining whereas 34 stained intensely for this protein. Involucrin expression was found to be associated with histological grade with those patients expressing involucrin tending to have well differentiated tumours and those not expressing this parameter tending to have poorly differentiated tumours (P = 0.045). There were no other associations between host and tumour factors and the various biological parameters. Survival analysis demonstrated that patients with an involucrin count above the median value had a better 5-year survival than those below the median (89% and 56% respectively) (P < 0.05). In addition, patients with no (or poor) involucrin expression had an increased risk of developing a recurrence at the primary site (P < 0.05). Involucrin appears to be a promising marker of tumour differentiation and survival in squamous carcinoma of the larynx.

MIB1 growth fraction is not related to prognosis in cervical squamous cell carcinoma treated with radiotherapy.

A monoclonal antibody, MIB1, recognizes Ki-67 antigen in routinely processed paraffin sections after microwave treatment. Cycling cells are positive for MIB1, and quiescent cells are negative for MIB1. MIB1 index represents the growth fraction of the cell population. Cervical biopsies taken from 186 patients with stage III squamous cell carcinoma prior to radiotherapy were investigated for MIB1 reactivity using an immunohistochemical method. Cancer cells that were positive for MIB1 showed an intranuclear or chromosomal positive pattern. The median MIB1 index was 43% (range, 18-74%). Of 186 patients, 87 had a MIB1 index of > 43% and the other 99 had an index of < 43%. The 5-year survival rates were 58% (50 of 87 patients) in the former group and 58% (57 of 99 patients) in the latter group. The chi 2 test indicated that no significant prognostic correlation existed between two groups (p = 0.989). We conclude that the MIB1 index demonstrates a considerable variation among patients and is not a predictive indicator of survival for patients with stage III cervical squamous cell carcinoma.