Radically resected pituitary adenomas: prognostic role of Ki 67 labeling index in a monocentric retrospective series and literature review

Chiloiro, Sabrina; Bianchi, Antonio; Doglietto, Francesco; Waure, Chiara de; Giampietro, Antonella; Fusco, Alessandra; Iacovazzo, Donato; Tartaglione, Linda; Nardo, Francesco Di; Signorelli, Francesco; Lauriola, Libero; Anile, Carmelo; Rindi, Guido; Maira, Giulio; Pontecorvi, Alfredo; Marinis, Laura De

doi:10.1007/s11102-013-0500-6

Cited by 43 publications

(34 citation statements)

References 37 publications

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“…In a previous work [22], in a series of 191 radically resected typical pituitary adenomas, we suggested that a Ki-67 value of 1.5% correlates with worse DFST. According to these previous data, we divided the study population of this series into two groups (group A: cases with a Ki-67 value <1.5%, and group B: cases with a Ki-67 value ≥1.5%) and, consequently, we analyzed epidemiological, clinical, histopathological, neuroradiological and prognostic features of pituitary adenomas with a Ki-67 expression higher and lower than 1.5%.…”

Section: Resultsmentioning

confidence: 86%

“…Recurrence was defined as hormonal and/or radiological disease relapse in functioning pituitary adenomas and radiological disease relapse in nonfunctioning pituitary adenomas [18,19,20,21,22]. Progression was defined as regrowth in tumor size based on MRI and/or evidence of an increase in plasma hormone levels in partially resected secreting pituitary adenomas [14,23].…”

Section: Methodsmentioning

confidence: 99%

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Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

et al. 2015

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Background and Objective: In 2004, the World Health Organization defined atypical pituitary adenomas as those with a Ki-67 expression >3%, an excessive p53 expression and increased mitotic activity. As the usefulness of this classification is controversial, we reviewed typical and atypical pituitary adenomas to compare the clinical and prognostic features. Patients and Methods: We retrospectively reviewed 343 consecutive pituitary adenomas. Atypical pituitary adenomas represented 18.7% of cases. All patients were operated on at the Department of Neurosurgery of our institution and were followed up at the Hypothalamic-Pituitary Disease Unit of the same institution. The median follow-up time was 75 months (range 7-345). Results: Younger age at diagnosis as well as immunohistochemical positivity for adrenocorticotropic hormone and prolactin correlated with a higher risk of atypical pituitary adenomas, whereas typical and atypical pituitary adenomas did not differ with regard to gender, tumor size, recurrence risk and disease-free survival time (DFST). Among the 219 patients who underwent radical surgery, a Ki-67 expression ≥1.5% was associated with a higher risk of recurrence and a worse DFST, even after correction for age at diagnosis, gender, immunohistochemical classification, tumor size, invasiveness and Knosp classification [p = 0.01; hazard ratio (HR) 2.572; 95% confidence interval (CI) 1.251-5.285). Pituitary adenomas with a Ki-67 expression ≥1.5% showed a worse DFST as compared to pituitary adenomas with a Ki-67 expression <1.5% (HR 2.166; 95% CI 1.154-4.064). Conclusion: In this series, atypical and typical pituitary adenomas did not differ with regard to recurrence and DFST. Pituitary adenomas with a Ki-67 expression ≥1.5% showed a higher recurrence risk and a worse DFST as compared to those with a Ki-67 expression <1.5%. We suggest that a Ki-67 expression ≥1.5% may be useful as a prognostic marker, though this will need to be confirmed by prospective, multicenter data.

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Section: Resultsmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

et al. 2015

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“…However, several studies did not confirm the correlation of these criteria with clinical behavior and aggressiveness of each individual adenoma (4,5,6,7,8,9,10). In particular, the Ki-67 LI, widely used to determine cellular growth fraction in many types of tumors, is accepted as prognostic indicator in pituitary tumors, although controversial results have emerged from clinical studies and criticisms are also reported in the literature (6,11,12,13,14,15). Other markers have been proposed to assess the aggressiveness of PA, among which pituitary tumor transforming gene, p27, p16, galectin-3, and cyclin D1, but none of them has gained general acceptance as prognostic indicator (9,16,17,18,19,20).…”

Section: Introductionmentioning

confidence: 99%

Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients

Coli

Sylvia

Fadda

et al. 2016

European Journal of Endocrinology

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Background: Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintenance 7 (MCM7), a cell-cycle regulator protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA. Design and methods: In this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated. Results: Twenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan-Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (R15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (!15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression. Conclusions: Data from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.

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Section: Discussionmentioning

confidence: 99%

“…Tumor cells proliferation is an important biological parameter that reflects disease behavior, which might also predicts for disease prognosis. The nuclear protein Ki-67 is a proliferative marker and widely used prognostic indicator in several cancer diagnosis, including breast cancer, bladder cancer, gastrointestinal neuroendocrine tumor, oral cancer, lung cancer, astrocytoma, and pituitary adenoma [8][9][10][11][12]23,24].In endometrial cancers, Ki-67 in addition to other biomarkers was found to be useful marker to distinguish benign proliferative conditions from cancer precursors and low grade endometrioid adenocarcinomas (16,25). In a study on 270 endometrial samples Ki-67 expression was found to be higher in samples with high-grade endometrioid carcinomas vs normal endometrial samples [26].…”

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Can Ki-67 Predict Pelvic Node Status in Endometrial Adenocarcinoma?

2016

J Cancer Sci

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Background: The Ki-67 marker is a nuclear protein that has a direct correlation with the degree of cells proliferation that often expressed in human neoplasm.Objective: To evaluate utilization of Ki-67 expression as predictor for pathological nodal positivity in endometrial endometrioid adenocarcinoma.Design: A retrospective case control study. Settings: Tertiary cancer center. Materials and methods:We evaluated 12 histopathological slides for patients with endometrioid adenocarcinoma of the uterus for percentage of expression of Ki-67. We defined high expression as Ki-67 stained > 50% of tumor cells. Main outcome measures:The correlation of Ki-67 high expression rates and pelvic node positivity in endometrioid adenocarcinoma.Results: Our sample mean age at diagnosis is (58.25 years) and median age is (57 years). The rate of high expression of Ki-67 in tumor cells among cases with positive lymph nodes vs controls were significantly higher (83%) vs (17%), with (p-value = 0.04). There were no significant differences between the mean age in cases and controls (59.8 vs 56.67) with (p = 0.67), tumor grade (p = 0.3), myometrium invasion (p = 0.1), cervical stromal invasion (p = 0.2), lymphovascular invasion (p = 0.2). On multivariate analysis a high expression of Ki-67 continued to be independent predictor for lymph node positivity (p = 0.02). Conclusions:This finding suggests that a high expression of Ki-67 plays an important role as predictor for lymph node positive in endometrioid adenocarcinoma. The level of expression of Ki-67 can be utilized for preoperative or postoperative risk assessment to predict for lymph node metastasis for cases with borderline indications for postoperative pelvic irradiation. Further prospective larger study is needed to validate this preliminary data. Page -02 ISSN: 2377-9292 adenocarcinoma of the uterus. The study was conducted in tertiary cancer center at King Abdullah Medical City. The protocol was reviewed and approved by institutional review board. Population was identified via search of hospital Electronic Medical Records between June of 2014 and June of 2016. We identified 48 cases with endometrial adenocarcinoma, then we identified 6 cases with pelvic node positive disease with no distance metastasis and we identified 6 matched controls of node negative. We match the cases and control for age and other clinicopathological characteristics including: tumor grade, lymphovascular space invasion, myometrial invasion and cervix invasion. The Immunohistochemical stain of Ki-67 was carried on unstained pathological slides taken from formalin-fixed, paraffinembedded tissues by standard automated immunohistochemistry on Ventana machine.We defined high expression as Ki-67 staining > 50% of tumor cells. All readings of the percentage of Ki-67 were carried out by one pathologist to overcome observers' variation (Figures 1 and 2). Statistical analysisCollected data was transferred and analyzed by using SPSS ver. 24 (SPSS Inc.). The correlation of high expression of Ki-67 with pelv...

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Radically resected pituitary adenomas: prognostic role of Ki 67 labeling index in a monocentric retrospective series and literature review

Cited by 43 publications

References 37 publications

Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

Typical and Atypical Pituitary Adenomas: A Single-Center Analysis of Outcome and Prognosis

Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients

Can Ki-67 Predict Pelvic Node Status in Endometrial Adenocarcinoma?

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