Ki-67 Labeling Index And Knosp Classification Of Pituitary Adenomas

Objective The World Health Organization recently published the 2017 classification of pituitary adenomas.They emphasized that there may be some relationship between pituitary adenomas with a high Ki-67 index(>3%)and aggressive tumor behavior.The MIB-1 labeling index,using the MIB-1 monoclonal antibody that recognizes the cell cycle-specific antigen Ki-67,is correlated with increased growth rate and invasive growth[2].Although most pituitary adenomas(PAs)are known to behave as benign tumors,efforts have been made to establish the clinical behavior of individual tumors,with emphasis on predicting those that might behave more aggressively.Here,The World Health Organization propose to define high-risk pituitary adenomass with a high Ki-67 labeling index,frequent recurrence,resistance to conventional treatments and/or temozolomide,growing rapid,and invading into the cavernous sinus segment of the internal carotid artery.The Knosp classification categorizes tumor proximity to the cavernous sinus segment of the internal carotid artery,and thus is used to quantify invasion of the cavernous sinus.Grade 3 and 4 pituitary tumors are considered invasive[3].Invasion into the cavernous sinus is the most common cause for incomplete resection,resulting in a higher recurrence rate[4].High Knosp grade(>3)pituitary tumors,therefore,have a high risk of recurrenceMethods We retrospectively analyzed the records of 247 surgical patients with pituitary adenoma in the saddle area who were admitted to the General Hospital of NingXia Medical University from January 2015 to February 2019.Inclusion criteria were as follows:1)acceptance of the endoscopic endonasal resection technique;2)confirmation of the functional status and permanent diagnosis for each tumor by hormone testing and histopathology,respectively;3)pre-operative and post-operative pituitary magnetic resonance imaging(MRI):if an MRI was obtained from an outside institute,it was excluded from the postoperative MRI analysis;4)pre-operative and post-operative data for prolactinoma(PRL),adrenocorticotropic hormone(ACTH),growth hormone(GH),thyroid-stimulating hormone(TSH),and cortisol(COR)at 4 pm and 8 am;and 5)postoperative pituitary MRI follow-up performed at the outpatient clinic at 3 months,6 months and yearly thereafter(MRI at 1.5 T).The data are presented as means and ranges for not continuous variables,we used Spearman Rank Correlations.All data analysis documented here were performed using IBM SPSS(Version 17.0?Copyright IBM Corporation and othersl989.2013.).Statistical tests to assess differences between groups and associations between variables,included analyses of variance.First,we take Kolmogorov-Smirnova of 4 groups.Then an assessment of the relationship between the Ki-67 labeling index and Knosp classification grade between the 4 groups was tested with Spearman correlation coefficient P-values<0.05 were considered significantResults The level of Ki-67 expression did not show any significant relationship with sex and age.There were statistical significance in the 3 groups:the Ki-67 labeling index and Knosp grade for functional pituitary adenomas and nonfunctional pituitary adenoma(Spearman correlation coefficient in functional pituitary adenomas r=-0.59,p<0.001 n=75 and r=0.367,p<0.01 n=168 in nonfunctional pituitary adenoma),and the Ki-67 labeling index>3%r=0.35,p<0.01 n=56Conclusion We have suggested that the negative correlation between the Ki-67 labeling index and Knosp grade in FPAs is a clinical manifestation rather than evidence that high proliferation index is associated with low invasive behavior of tumors.The early clinical hormonal symptoms of functional pituitary adenomas that are associated with high Ki-67 labeling,allow less time for tumors to grow.In addition,it is challenging to manage the functional pituitary tumors since they tend to recur quickly following initial treatment and are generally unresponsive to therapy.We recommend that patients with symptoms of hormonal imbalances seek advice in outpatient clinics as soon as possible to increase the frequency of procedures to successfully arrest the invasive behavior of functional pituitary adenomas.If patients with clinical hormonal symptoms rapidly deteriorate in a short time,we should consider whether the value of Ki-67 labeling is high Delayed treatment may come up with a poor prognosis and limited therapeutic options.Early treatment may improve gross total resection rate,with beneficial therapeutic effects.For NFPAs,improving gross total resection rate to avoid recurrence is the key of treatment.When postoperative immunohistochemistry showed that nonfunctional pituitary adenoma with high Ki-67 labeling index,increase the frequency of re-examination was recommended.The high Ki-67 labeling index in tissue samples suggests the need for careful clinical and radiological follow-up.