Dataset Information

Phosphorylated EGFR (pEGFR T693) as a Novel Predictor of Recurrence in Non-Functioning Pituitary Adenomas.

ABSTRACT:

Purpose

Non-functioning pituitary adenomas (NFPAs) exhibit high recurrence rates after surgery. However, the determinants of recurrence are inconsistent in the available literature. The present study sought to investigate the association between nuclear phosphorylated EGFR (pEGFR) levels and recurrence of NFPAs.

Methods

Tissue microarrays from patients undergoing adenomectomy for NFPAs at our tertiary care center from 2003 to 2015 and having a minimum of 60 months of follow-up (n=102) were accessed. Immunohistochemical analysis (IHC) was performed to determine the expression of nuclear pEGFR T693. h-score was calculated as the product of staining intensity and the number of positively staining cells. Radiological surveillance (MRI) was performed to categorize NFPAs as recurrent or non-recurrent on follow-up.

Results

The mean age of the cohort was 50 ± 11 years with a male preponderance (61.1%). Recurrence was observed in 46.1% of the patients at a median of 123 months (IQR 72-159) of follow-up. pEGFR T693 positivity was higher in a significantly greater number of recurrent NFPAs as compared to non-recurrent NFPAs (95.7% vs 81%, p=0.02). h-scores were also significantly higher in recurrent NFPAs (122.1 ± 6 vs 81.54 ± 3.3, p<0.0001). pEGFR T693 positivity significantly predicted recurrence in NFPAs (HR=4.9, CI 2.8-8.8, p<0.0001). ROC analysis revealed an h-score cutoff of 89.8 as being associated significantly with recurrence (sensitivity 80%, specificity 78%, AUC 0.84, p<0.0001).

Conclusion

pEGFR T693 was expressed in significantly higher number of recurrent NFPAs. The h-scores were also higher in recurrent NFPAs. Nuclear pEGFR T693 may serve as a predictor of recurrence in NFPAs.

SUBMITTER: Rai A

PROVIDER: S-EPMC8289705 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).