scholarly journals Evaluation of prognostic utility of MIB-1 and p53 expression in pituitary adenomas: correlations with clinical behaviour and follow-up results

2014 ◽  
Vol 28 (3) ◽  
pp. 502-507 ◽  
Author(s):  
Asen Hadzhiyanev ◽  
Radina Ivanova ◽  
Emil Nachev ◽  
Atanaska Elenkova ◽  
Maria Yaneva ◽  
...  
Author(s):  
Kent Tadokoro ◽  
Colten Wolf ◽  
Joseph Toth ◽  
Cara Joyce ◽  
Meharvan Singh ◽  
...  

Abstract Objectives Ki-67/MIB-1 is a marker of cellular proliferation used as a pathological parameter in the clinical assessment of pituitary adenomas, where its expression has shown utility in predicting the invasiveness of these tumors. However, studies have shown variable results when using Ki-67/MIB-1 association with recurrence. The purpose of this study is to determine if a high Ki-67/MIB-1 labeling index (LI) is predictive of recurrence in pituitary adenomas. Methods A retrospective chart review was performed for patients undergoing pituitary adenoma resection with at least 1 year of follow-up. Additionally, systematic data searches were performed and included studies that correlated recurrence rate to Ki-67/MIB-1 LI. Our institutional data were included in a synthesis with previously published data. Results Our institutional review included 79 patients with a recurrence rate of 26.6%. We found that 8.8% of our patients had a high Ki-67/MIB-1 LI (>3%); however, high Ki-67/MIB-1 was not associated with recurrence. The systematic review identified 244 articles and 49 full-text articles that were assessed for eligibility. Quantitative analysis was performed on 30 articles including our institutional data and 18 studies reported recurrence by level of Ki-67/MIB-1 LI. Among studies that compared Ki-67/MIB-1 ≥3 vs. <3%, 10 studies reported odds ratios (OR) greater than 1 of which 6 were statistically significant. A high Ki-67/MIB-1 had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% confidence interval [CI]: 2.31–7.42). Conclusion This systematic review suggests that a high Ki-67/MIB-1 should prompt an increased duration of follow-up due to the higher odds of recurrence of pituitary adenoma.


2011 ◽  
Vol 114 (2) ◽  
pp. 336-344 ◽  
Author(s):  
Gabriel Zada ◽  
Whitney W. Woodmansee ◽  
Shakti Ramkissoon ◽  
Jordan Amadio ◽  
Vania Nose ◽  
...  

Object The 2004 WHO classification of pituitary adenomas now includes an “atypical” variant, defined as follows: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity. The authors review the incidence of this atypical histopathological subtype and its correlation with tumor subtype, invasion, and surgical features. Methods The records of 121 consecutive patients who underwent transsphenoidal surgery for pituitary adenomas during an 18-month period were retrospectively reviewed for evidence of atypical adenomas. Results Eighteen adenomas (15%) met the criteria for atypical lesions; 17 (94%) of the 18 were macroadenomas. On imaging, 15 (83%) demonstrated imaging evidence of surrounding invasion, compared with 45% of typical adenomas (p = 0.004). Atypical tumors occurred in 12 female (67%) and 6 male (33%) patients. Patient age ranged from 16 to 70 years (mean 48 years). Nine patients (50%) had hormonally active tumors, and 9 had nonfunctional lesions. Four (22%) of the 18 patients presented to us with recurrent tumors. Immunohistochemical analysis demonstrated the following tumor subtypes: GH-secreting adenoma with plurihormonal staining (5 patients [28%]); null-cell adenoma (5 patients [28%]); silent ACTH tumor (3 patients [17%]), ACTH-staining tumor with Cushing's disease (2 patients [11%]), prolactinoma (2 patients [11%]), and silent FSH-staining tumor (1 patient [6%]). The MIB-1 labeling index ranged from 3% to 20% (mean 7%). Conclusions Atypical tumors were identified in 15% of resected pituitary adenomas, and they tended to be aggressive, invasive macroadenomas. More longitudinal follow-up is required to determine whether surgical outcomes, potential for recurrence, or metastasis of atypical adenomas vary significantly from their typical counterparts.


Author(s):  
Stephen J. Hentschel ◽  
Ian E. McCutcheon ◽  
Wayne Moore ◽  
Felix A. Durity

ABSTRACT:Background:P53 expression and increased MIB-1 proliferation index have been shown to correlate with invasive behavior in pituitary adenomas. The purpose of this study was to determine whether these indices could be used to predict a higher likelihood of recurrence in clinically nonfunctional pituitary adenomas and thus guide adjuvant therapy.Methods:Fifty-one clinically nonfunctional pituitary adenomas were selected from the database at the Vancouver Hospital and Health Sciences Center between the years 1990-1998. Included were 32 nonrecurrent and 19 recurrent adenomas.Results:The mean initial labelling index for p53 in nonrecurrent tumours was 0.38% (0-1.58%), while it was 0.46% (0-3.65%) for recurrent adenomas. The mean initial MIB-1 index for nonrecurrent tumours was 1.63% (0.08-9.36%), while for recurrent tumours it was 1.92% (0-7.76%). The percentage of p53 positive adenomas was 66% for nonrecurrent tumours and 68% for recurrent tumours. None of the differences in the labelling indices between the recurrent and nonrecurrent groups was statistically significant. As 12 patients (38%) in the nonrecurrent group had undergone radiotherapy as initial adjuvant therapy after surgery and none of the recurrent group had done so, patients who did not receive radiotherapy in the nonrecurrent group were analyzed separately. Again, none of the differences in the labelling indices between the recurrent and nonrecurrent groups was statistically significant when the effect of radiotherapy was removed from the analysis.Conclusions:The results demonstrate no statistical difference in the p53 or MIB-1 labelling indices between recurrent and nonrecurrent nonfunctional pituitary adenomas. Concern should be raised in attaching too much clinical significance to these labelling indices, especially with respect to p53 as a predictor of the clinical behavior of nonfunctional pituitary adenomas.


Neurosurgery ◽  
2017 ◽  
Vol 83 (4) ◽  
pp. 602-610 ◽  
Author(s):  
Kelsi Chesney ◽  
Zoe Memel ◽  
Dhiraj J Pangal ◽  
Daniel Donoho ◽  
Kyle Hurth ◽  
...  

Abstract BACKGROUND Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology. OBJECTIVE To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence. METHODS A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth. RESULTS Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression. CONCLUSION Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.


2013 ◽  
Vol 74 (S 01) ◽  
Author(s):  
Eric Monsalves ◽  
Soroush Larjani ◽  
Bruno Godoy ◽  
Boris Krischek ◽  
Kyle Juraschka ◽  
...  

2003 ◽  
Vol 111 (06) ◽  
Author(s):  
C Tanase ◽  
E Codorean ◽  
C Ardeleanu ◽  
D Terzea ◽  
G Butur ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Chan ◽  
W Dinsfriend ◽  
J Kim ◽  
R Steingart ◽  
J.W Weinsaft

Abstract Background LGE-CMR tissue characterization is widely used to identify cardiac masses (CMASS) in cancer patients – including neoplasm (NEO) and thrombus (THR). Prognostic utility of their differential LGE patterns is unknown. Purpose To determine incremental prognostic utility of LGE patterns in CMASS Methods The population comprised of cancer patients with CMASS on LGE-CMR, for which etiology was classified based on presence (NEO) or absence (THR) of enhancement, and controls matched for cancer type/stage. LGE-CMR tissue properties of NEO was classified based on extent of contrast enhancement – diffusely enhancing (DE), mixed (ME), and predominantly avascular (PA). Clinical follow up was performed for embolic events within 6 months of CMR and all-cause mortality. Results 330 cancer patients (55% M; 55±16yo) with an array of cancer diagnoses (19% sarcoma, 17% GI, 13% GU) were studied. Among CMASS+ pts (n=190), 66% had NEO and 34% had THR on LGE. All THR were non-enhancing. Among NEO, LGE pattern was variable (46% DE, 41% ME, 13% PA); ME lesions were larger than other groups (Fig. 1A). Quantitative tissue properties were consistent with qualitative groups, as evidenced by stepwise variation in signal intensity and CNR. Cumulative embolic events were 3-fold higher in CMASS+ than controls (All: 20% vs. 7%, p=0.001; PE: 13% vs. 5%, p=0.02; CVA/systemic embolism: 10% vs. 3%, p=0.01). Median time to event was 1.3 months [IQR 0.1–2.3] from CMR. Aggregate events were similar between NEO and THR, reflecting similar rates of PE and CVA (p=NS). Among CMASS pts with embolic events, 56% were on anticoagulation at time of event (59% NEO, 50% THR, p=0.61). Regarding CMASS morphology, emboli were 3-fold higher among intracavitary (IC) or highly mobile (HM) CMASS (IC: 25% vs 7%, p&lt;0.001; HM: 38% vs 12%, p=0.001). Regarding location, right sided CMASS were associated with a 3–5 fold increase in PE (IC: 19% vs 6%; HM: 35% vs 7%, both p&lt;0.001) and similar CVA events among left sided CMASS (IC: 17% vs. 6%, p=0.02; HM: 33% vs 6%, p=0.05). Embolic events were similar when partitioned based on quantitative LGE patterns between patients with and without embolic events. As for all-cause mortality, NEO on CMR conferred increased mortality than THR (HR 3.06 [CI=1.84–5.1], p&lt;0.001) and matched controls (HR 2.08 [CI=1.42–3.04], p&lt;0.001) during a median follow-up of 9.4 months [IQR 3.6–23.2]. Among NEO subgroups (Fig. 1B), survival was lower in patients with heterogeneous LGE patterns vs matched controls: the lowest survival in ME (p=0.002) suggests increased vascularity and tumor hypoxia/necrosis associated with aggressive tumors and hence larger lesions. Conclusions Among cancer patients, CMR-evidenced CMASS confers high short-term embolic risk, which are equivalently common between NEO and THR. Intra-cavitary location and increased mobility augment embolic risk irrespective of CMASS tissue properties whereas differential LGE patterns on CMR strongly impact prognosis. Funding Acknowledgement Type of funding source: None


Neurosurgery ◽  
2015 ◽  
Vol 79 (3) ◽  
pp. 406-417 ◽  
Author(s):  
Sean M. Barber ◽  
Bin S. Teh ◽  
David S. Baskin

Abstract BACKGROUND Early results of postoperative fractionated stereotactic radiotherapy (FSRT) for functional and nonfunctional pituitary adenomas appear promising, but the majority of available evidence draws from small series with insufficient follow-up data to draw meaningful conclusions. OBJECTIVE To evaluate the long-term outcomes of a large series of patients undergoing FSRT for both functional and nonfunctional pituitary adenomas with the Novalis system (Brain LAB, Heimstetten, Germany). METHODS Chart data for 75 consecutive patients undergoing FSRT for a pituitary tumor (21 functional and 54 nonfunctional adenomas) at our institution between January 2004 and June 2013 were reviewed. RESULTS Radiographic progression-free survival was 100% over a mean of 47.8 months of radiographic follow-up (range, 12.0-131.2 months). Hormonal normalization was seen in 69.2% of patients with functional adenomas after FSRT, whereas 30.8% experienced partial hormonal control. Mild, grade I acute adverse effects were observed during radiotherapy treatment in 36 patients (48%), and objective, persistent worsening of vision occurred in a single patient (1.5%) after FSRT. New hormonal deficits were seen in 28.0% of patients after FSRT. Radiographic responses were inversely related to tumor volume. CONCLUSION FSRT delivers radiographic and functional outcomes similar to those seen with stereotactic radiosurgery and conventional radiotherapy with less resultant toxicity. FSRT is most beneficial for smaller tumors (those &lt;3 cm in diameter).


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