Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery

Dubois, Séverine; Guyétant, Serge; Menei, Philippe; Rodien, Patrice; Illouz, Frédéric; Vielle, Bruno; Rohmer, V.

doi:10.1530/eje-07-0099

Cited by 55 publications

(52 citation statements)

References 50 publications

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“…20) Some studies also demonstrated a correlation between MIB-1 labeling index and re-growth or recurrence, 9,14,30,32) but other studies found no such correlations. 5,13,24,27) These discrepancies and differences between estimates of the threshold MIB-1 labeling index may be attributable to variations in the definition of recurrence or progression. 26) Another possible source of differences or discrepancies is the method used to count the labeled cells.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, some other studies did not show any significant correlation between MIB-1 index and CS invasion. 1,5,14,22,28,33) Whether invasive potential affects progression remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…8,18) Various attempts have been made to establish markers that correlate with the clinical behavior of pituitary adenomas, such as invasion, recurrence, or malignancy. 1,2,5,[7][8][9][10][12][13][14][15]17,[19][20][21][22][23][24][27][28][29][30][31][32][33] Among the available methods of growth fraction determination, Ki-67 is a reliable marker for growth fraction determination of various specific cell cycle antigens. 1,12,32) Ki-67 is a protein which reacts with a …”

Section: Introductionmentioning

confidence: 99%

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Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas: Correlations With Clinical Variables

Matsuyama

2012

Neurol. Med. Chir.(Tokyo)

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Reliable prognostic parameters indicating progression in residual pituitary adenoma after surgery are necessary. The World Health Organization classification of tumors of endocrine organs defines atypical pituitary adenomas as tumor with Ki-67 labeling index higher than 3%, excessive p53 immunoreactivity, and increased pleomorphism. The real value of Ki-67 labeling index correlating with tumor progression is controversial. We investigated the relationship between positive labeling for MIB-1 and clinical features of 39 patients with pituitary adenomas with and without rapid re-growth after initial surgery. Ki-67 expression revealed pituitary adenomas with progression (re-growth within 5 years after initial surgery) had a mean proliferation index of 3.66 ± 3.00% (mean ± standard deviation [SD], n ＝ 12), which was significantly higher than in tumors without progression of 1.89 ± 1.25% (mean ± SD, n ＝ 27) (p º 0.05, Mann-Whitney test). Receiver operating characteristic analysis showed a threshold level of Ki-67 expression greater than 2.0% predicts progression with high specificity. Younger patients had higher MIB-1 index and more progression (p º 0.05). Adenomas with cavernous sinus invasion, functioning adenomas, and giant adenomas had higher MIB-1 index (p º 0.05). There was no significant correlation between tumor size or cavernous sinus invasion and progression. More completely removed tumors were less progressive. A threshold of 2% for the MIB-1 labeling index predicts higher risk of progression of residual adenomas after surgery, so shorter interval of follow-up neuroimaging, and early initiation of adjuvant therapy might be required.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas: Correlations With Clinical Variables

Matsuyama

2012

Neurol. Med. Chir.(Tokyo)

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“…The protein expression of Ki-67 was examined by immunohistochemical staining in 91 invasive pituitary tumors. The Ki-67 labeling index (LI) was calculated as the ratio of the labeled over total nuclear areas (Dubois et al 2007). …”

Section: Immunohistochemistrymentioning

confidence: 99%

Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors

Lin¹,

Jiang²,

Ye³

et al. 2009

Endocrine-Related Cancer

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Genetic alterations in the PIK3CA gene of the phosphoinositide 3-kinase (PI3K)/AKT pathway have been found in many human tumors, but they have not been explored in pituitary tumors. We undertook the present study to explore mutations and amplifications of the PIK3CA gene in pituitary tumors. DNA sequencing and real-time quantitative PCR were used to examine mutations and amplifications respectively, on genomic DNA samples isolated from 353 cases of pituitary tumors, and immunohistostaining was used to assess PIK3CA expression. About 8 out of 91 (9%) invasive pituitary tumors versus 0 out of 262 (0%) noninvasive tumors were found to harbor somatic mutations in exons 9 and 20 of the PIK3CA gene (P!0.001), and the mutation was associated with increased disease recurrence. Genomic PIK3CA amplifications (defined as R4 copies) were observed in both invasive and noninvasive tumors, with a prevalence of around 20-40% in various types of pituitary tumors. PIK3CA protein overexpression was observed in cases with high PIK3CA copy number. RAS mutations were also examined and found in 6 out of the 91 (7%) invasive tumors. PIK3CA amplifications were mutually exclusive with PIK3CA or RAS mutations (P!0.001). This study demonstrated for the first time relatively common PIK3CA mutations and amplifications as well as RAS mutations and their tendency of mutual exclusivity in pituitary tumors. The data provide strong genetic evidence supporting a role of the PI3K/AKT signaling pathway in the tumorigenesis of pituitary tumors, particularly the invasive types.

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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).…”

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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Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery

Cited by 55 publications

References 50 publications

Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas: Correlations With Clinical Variables

Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas: Correlations With Clinical Variables

Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors

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

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