Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space

Abstract

The preoperative diagnosis of cavernous sinus invasion remains difficult and controversial, and there are currently no reliable histological or molecular markers that predict pituitary tumour behaviour and response to treatment. We evaluated 45 patients with pituitary adenoma. The results have shown that the sensitivity of MRI for indicating cavernous sinus invasion in this prospective study was 60%, specificity 85%, positive predictive value 83.33%, negative predictive value 62.96%. Forty-five specimens of pituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, bcl-2, nm23 and MMP-9 immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. The results have shown that MVD of invasive pituitary adenomas was significantly higher than that of noninvasive (P < 0.001). There was an association between the invasion of pituitary adenomas and Ki-67 LI (P = 0.039) or the expression of VEGF (P < 0.001) and MMP-9 (P < 0.001). But c-myc LI and bcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 vs. P = 0.201). On the other hand, there is an inverse relationship between nm23 expression and tumor invasion (P < 0.001). In conclusion, parasellar extension of pituitary adenomas through the medial wall of the cavernous sinus diagnosed at surgery, can be determined by radiology with sensitive gadolinium-enhanced MRI. Although our study has shown that MVD and the expression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas, they are lack of specificity. These markers can only provide some useful informations on the therapeutic strategy of pituitary adenomas.

Influence of parasellar extension of macroprolactinomas defined by magnetic resonance imaging on their responsiveness to dopamine agonist therapy

“…These modifications interrupt the normal inhibitory effects of dopamine on lactotroph secretion and proliferation, and DA‐resistant tumours have been found to exhibit mitotic activity and a high Ki‐67 labelling index 8 . Although the mechanisms of invasiveness of pituitary adenomas are still poorly understood, 9 a possible explanation for our results is that the higher proliferative activity of DA‐resistant tumours contributes to their invasive potential.…”

“…This CS invasion has been recognized as the most reliable feature of pituitary tumour aggressiveness 5,6 . It has been associated with high hormone levels in functioning adenomas, 7 elevated proliferative activity as measured by the Ki‐67 labelling index, 3,8,9 lower surgical cure rate and increased postoperative morbidity, mainly optic nerve damage and anterior pituitary function deficits 10 …”

Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas

“…Secondly, although there are widely recognized diagnostic criteria of modified Hardy's classification and Knosp's classification for IPAs, making a definite diagnosis is still difficult because of unavoidable false negative and false positive results. [56] Thirdly, there may be differences in detection methods of IHC among different laboratories.…”

Biomarkers of aggressive pituitary adenomas

“…87%); however, the Ki-67 index was not significantly different in the subgroup of adenomas with invasion of the cavernous sinus compared with groups with other types of invasion. Nevertheless, the ability of the Ki-67 index to predict tumor invasiveness is somewhat controversial as others have found no difference in Ki-67 expression in invasive pituitary adenomas (Yonezawa et al 1997, Lath et al 2001, Paek et al 2005, Pan et al 2005, Wierinckx et al 2007). …”