Prognostic Significance of the Ki-67 Labeling Index in Growth Hormone-Secreting Pituitary Adenomas

Fusco, Alessandra; Zatelli, Maria Chiara; Bianchi, Antonio; Cimino, Vincenzo; Tilaro, L.; Veltri, Flora; Angelini, Flavia; Lauriola, Libero; Vellone, Valerio Gaetano; Doglietto, Francesco; Ambrosio, Maria Rosaria; Maira, Giulio; Giustina, Andrea; Uberti, Ettore C. degli; Pontecorvi, Alfredo; Marinis, Laura De

doi:10.1210/jc.2008-0126

Cited by 91 publications

(71 citation statements)

References 14 publications

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“…Previous results from our group showed that the Ki-67 is significantly higher in resistant tumours (23). The absence of adenomas with higher Ki-67 in this independent case series might account for these results.…”

Section: European Journal Of Endocrinologysupporting

confidence: 73%

“…Ki-67 labelling index (LI) was evaluated, in each case, in at least five non-overlapping representative areas counting at least 1000 cells, as previously reported (23).…”

Section: Histopathological Studiesmentioning

confidence: 99%

“…Numerous factors are associated with resistance to first-generation SSAs (10), including reduced expression of SSTR2a (11,12,13,14,15,16,17,18), sparsely granulated adenoma subtype (19,20,21,22) and a higher Ki-67 proliferation index (23,24). Adenomas that occur in patients with AIP mutations and AIP mutation-negative sporadic somatotroph adenomas with reduced AIP expression show increased invasiveness (25,26,27,28) and are frequently resistant to first generation SSAs (29).…”

Section: Introductionmentioning

confidence: 99%

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Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Iacovazzo

Carlsen²,

Lugli

et al. 2016

European Journal of Endocrinology

135

109

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Aim: To gather data regarding factors predicting responsiveness to pasireotide in acromegaly. Patients and methods: SSTR2a, SSTR3, SSTR5, AIP, Ki-67 and the adenoma subtype were evaluated in somatotroph adenomas from 39 patients treated post-operatively with somatostatin analogues (SSAs). A standardized SSTR scoring system was applied (scores 0-3). All patients received first-generation SSAs, and 11 resistant patients were subsequently treated with pasireotide LAR. Results: None of the patients with negative or cytoplasmic-only SSTR2a expression (scores 0-1) were responsive to firstgeneration SSAs, as opposed to 20% (score 2) and 50% of patients with a score of 3 (PZ0.04). None of the patients with an SSTR5 score of 0-1 were responsive to pasireotide, as opposed to 5/7 cases with a score of 2 or 3 (PZ0.02). SSTR3 expression did not influence first-generation SSAs or pasireotide responsiveness. Tumours with low AIP were resistant to first-generation SSAs (100 vs 60%; PZ0.02), while they had similar responsiveness to pasireotide compared to tumours with conserved AIP expression (50 vs 40%; PZ0.74). Tumours with low AIP displayed reduced SSTR2 (SSTR2a scores 0-1 44.4 vs 6.7%; PZ0.006) while no difference was seen in SSTR5 (SSTR5 scores 0-1 33.3 vs 23.3%; PZ0.55). Sparsely granulated adenomas responded better to pasireotide compared to densely granulated ones (80 vs 16.7%; PZ0.04). Conclusion: The expression of SSTR5 might predict responsiveness to pasireotide in acromegaly. AIP deficient and sparsely granulated adenomas may benefit from pasireotide treatment. These results need to be confirmed in larger series of pasireotide-treated patients.

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Section: European Journal Of Endocrinologysupporting

confidence: 73%

“…Ki-67 labelling index (LI) was evaluated, in each case, in at least five non-overlapping representative areas counting at least 1000 cells, as previously reported (23).…”

Section: Histopathological Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Iacovazzo

Carlsen²,

Lugli

et al. 2016

European Journal of Endocrinology

135

109

View full text Add to dashboard Cite

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“…Recently, some novel genetic factors have been identified that predict difficult disease management in acromegaly. These newer factors, taken together with the standard pathological measures of tumor aggression such as granulation pattern, Ki-67 and gsp mutations can help to predict tumor responses to SSAs used postoperatively (Barlier et al 1998, Bhayana et al 2005, Fusco et al 2008. For instance, mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene lead to a significantly more aggressive phenotype in acromegaly including younger age at onset, larger tumor size, higher hormonal levels, and a significantly poorer response to SSA in terms of hormonal reduction and tumor shrinkage (Daly et al 2010).…”

Section: Discussionmentioning

confidence: 99%

T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly

Potorac

Pétrossians

Daly

et al. 2016

Endocrine-Related Cancer

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GH-secreting pituitary adenomas can be hypo-, iso-or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 23:113 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso-and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso-and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso-and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly.

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“…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%

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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Prognostic Significance of the Ki-67 Labeling Index in Growth Hormone-Secreting Pituitary Adenomas

Abstract: The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.

Cited by 91 publications

References 14 publications

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study

T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly

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

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