Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature

Guadagno, Elia; d’Avella, Elena; Cappabianca, Paolo; Colao, Annamaria; De, Marialaura Del Basso

doi:10.1007/s40618-020-01275-9

Cited by 19 publications

(10 citation statements)

References 215 publications

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“…They found significant associations between the Ki-67 labeling index and patient age, tumor size, nodal metastasis, distant metastasis, extrathyroid extension, and TNM stage. Furthermore, they confirmed that patients with a high Ki-67 labeling index had a poorer disease-free survival and increased risk of mortality than patients with a low Ki-67 labeling index [32,36]. However, earlier studies used less sensitive immunohistochemical methods and their absolute values are no longer comparable with those in recent studies, although their conclusions are overall consistent with our conclusion that the Ki-67 examination can identify curable carcinomas as cases with a low Ki-67 index.…”

Section: Risk Classification Of Thyroid Tumorsmentioning

confidence: 78%

“…The first study of the Ki-67 index focusing on PTCs was by Kjellman et al, and they demonstrated an association between a high Ki-67 index and more aggressive disease (recurrence, metastasis, and cancer death) [9], which was later confirmed by several authors [11][12][13][31][32][33][34][35][36]. The Ki-67 labeling index was reported to be an independent prognostic factor for recurrence [11,24,33,34] and cancer death [11,24].…”

Section: Risk Classification Of Thyroid Tumorsmentioning

confidence: 92%

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How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery—Risk stratification of papillary thyroid carcinoma in young patients—

et al. 2021

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Current histopathological diagnosis methods cannot distinguish the two types of thyroid carcinoma: clinically significant carcinomas with a potential risk of recurrence, metastasis, and cancer death, and clinically insignificant carcinomas with a slow growth rate. Both thyroid tumors are diagnosed as "carcinoma" in current pathology practice. The clinician usually recommends surgery to the patient and the patient often accepts it because of cancer terminology. The treatment for these clinically insignificant carcinomas does not benefit the patient and negatively impacts society. The author proposed risk stratification of thyroid tumors using the growth rate (Ki-67 labeling index), which accurately differentiates four prognostically relevant risk groups based on the Ki-67 labeling index, ≥30%, ≥10 and <30%, >5 and <10%, and ≤5%. Indolent thyroid tumors with an excellent prognosis have the following four features: young age, early-stage (T1-2 M0), curatively treated, and low proliferation index (Ki-67 labeling index of ≤5%), and are unlikely to recur, metastasize, or cause cancer death. Accurate identification of these indolent tumors helps clinicians select more conservative treatments to avoid unnecessary aggressive (total thyroidectomy followed by radio-active iodine) treatments. Clinicians can alleviate the fears of patients by confirming these four features, including the low proliferation rate, in a pathology report immediately after surgery when patients are most concerned.

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Section: Risk Classification Of Thyroid Tumorsmentioning

confidence: 78%

Section: Risk Classification Of Thyroid Tumorsmentioning

confidence: 92%

How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery—Risk stratification of papillary thyroid carcinoma in young patients—

et al. 2021

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“…This procedure has long been used to diagnose endocrine tumors, particularly pituitary adenomas. Guadagno E et al 31 conducted a fairly large study on the signi cance of Ki-67 in pituitary adenomas, with mixed results. Ki-67 is one component in assessing the proliferative nature of pituitary adenoma, according to WHO guidelines, so it must be combined with other markers to provide a better prognostic value.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic Factors Related to Post-Operative Outcome of Pituitary Adenoma: a Meta-Analysis

Tarigan

Alhabsyi

Kurniawan

2021

Preprint

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Purpose: About 30% to 40% of patients with pituitary adenoma require surgery. About 25% to 40% of those who have had surgery will have an aggressive outcome. The purpose of this study was to see if certain clinicopathologic factors such as size, type/subtype, invasiveness, proliferative (ki-67, mitotic rate, and p53), and grade influenced the aggressiveness of postoperative pituitary adenomas. Methods: The factors mentioned in the research objectives were examined as independent variables. Ten studies out of 736 were chosen. The 10 studies had 2727 participants and 632 cases. The monitoring lasted 3-11 years. The studies' quality ranged from fair to excellent. Results: The results of the meta-analysis were: size ≥10mm OR 1,79 (1,29-2,48), corticotroph OR 1,91 (1,41-2,58), invasive OR 3,67 (1,95-6,90), proliferative OR 4,78(3,61-6,32), Ki-67 ≥ 3% OR 4,13 (2,94-5,81), mitotic rate > 2 OR 3,91 (2,74-5,57), p53 positive OR 1,92 (1,28-2,90), and grade 2b OR 4,56 (3,0-6,91). Conclusions: Size, type/subtype, invasiveness, proliferative (ki-67, mitotic rate, and p53), and grade of postoperative pituitary adenoma influenced the postoperative aggressiveness outcome.

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“…Ki67 is a well-established marker of proliferation, with a cutoff of 3% being the most commonly used. However, its controversial role has been acknowledged and lower thresholds of 2% to 2.5% have been validated in some studies (17,18). Similarly, for invasiveness, radiological invasion is given more credence than histopathological evidence (4,17).…”

Section: A B Cmentioning

confidence: 99%

Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas

et al. 2021

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IntroductionAggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.MethodsThis was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.ResultsThe study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.ConclusionEarly initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.

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Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature

Cited by 19 publications

References 215 publications

How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery—Risk stratification of papillary thyroid carcinoma in young patients—

How to identify indolent thyroid tumors unlikely to recur and cause cancer death immediately after surgery—Risk stratification of papillary thyroid carcinoma in young patients—

Clinicopathologic Factors Related to Post-Operative Outcome of Pituitary Adenoma: a Meta-Analysis

Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas

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