MCM7 as a marker of postsurgical progression in non-functioning pituitary adenomas

in European Journal of Endocrinology
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  • 1 T Hallén, Department of Neurosurgery, Sahlgrenska University Hospital, Goteborg, Sweden
  • 2 D Olsson, Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
  • 3 C Hammarstrand, internal Medicine, Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
  • 4 C Örndal, Department of Pathology and Cytology, Skaraborgs Sjukhus Skövde, Skovde, Sweden
  • 5 A Engvall, Department of Neuroradiology, Sahlgrenska universitetssjukhuset, Goteborg, Sweden
  • 6 O Ragnarsson, Department of Endocrinology, Sahlgrenska University Hospital, Goteborg, Sweden
  • 7 T Skoglund, Department of Neurosurgery, Sahlgrenska universitetssjukhuset, Goteborg, Sweden
  • 8 G Johannsson, Internalmedicine and clinical nutrition, University of Gothenburg, Goteborg, Sweden

Correspondence: Tobias Hallén, Email: tobias.hallen@vgregion.se
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Objective: Current markers predicting tumour progression of pituitary adenomas after surgery are insufficient. Our objective was to investigate if minichromosome maintenance protein 7 (MCM7) expression predicts tumour progression in non-functioning pituitary adenomas (NFPAs).

Methods: In a cohort study of surgically treated NFPAs, two groups with distinctly different behaviour of a residual tumour were selected: one group requiring reintervention due to tumour progression (reintervention group, n=57) and one with residual tumours without progression (radiologically stable group, n=40). MCM7, Ki-67, estrogen receptor-⍺ expression, mitotic index and tumour subtype was assessed by immunohistochemistry and their association with tumour progression requiring reintervention was analysed.

Results: Median (IQR) MCM7 expression was 7.4% (2.4–15.2) in the reintervention group compared with 2.0% (0.6–5.3) in the radiologically stable group (P<0.0001). Cox regression analysis showed an association between high (>13%) MCM7 expression and reintervention (HR 3.1; 95%CI:1.7-5.4; P=0.00012). The probability for reintervention within 6 years for patients with high MCM7 was 93%. Ki-67 expression >3% (P=0.00062), age ≤55 years (P=0.00034) and mitotic index ≥1 (P=0.024) were also associated with reintervention. Using a receiver operating characteristics curve, a predictive model for reintervention with all the above predictors yielded an area under the curve of 82%. All eight patients with both high MCM7 and high Ki-67 needed reintervention.

Conclusion: This cohort study shows that expression of MCM7 is a predictor for clinically significant postoperative tumour progression. Together with age, Ki-67 and mitotic index, MCM7 might be of added value as a predictive marker when managing patients with NFPA after surgery.

 

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