Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy

Abstract

Gonadotroph tumors, although frequent, are poorly studied and understood, being usually included in the larger nonfunctioning pituitary neuroendocrine tumors (PitNETs) group. Moreover, in comparison to the other types of PitNETs, no established medical treatment is currently available for gonadotroph tumors. Here, we performed a retrospective study and analyzed the clinicopathological characteristics of 98 gonadotroph tumors operated in a single large pituitary center. Although being larger in men (p = 0.01), the aggressiveness of gonadotroph tumors did not appear to be sex-related. LH tumors were rare (4/98) and exclusively encountered in men. Somatostatin receptor type 5 (SST5) was absent in all analyzed tumors. The immunoreactive score (IRS) of somatostatin receptor type 2 (SST2) and of estrogen receptor alpha (ERα) was associated with the histological subtype (p = 0.01 and p = 0.02). IRS ERα correlated moderately with IRS SST2 in all (rho = 0.44, adjusted p-value = 0.0001) and in male (rho = 0.51, adjusted p-value = 0.0002) patients, and with follicle-stimulating hormone (FSH) percentage in all (rho = 0.40, adjusted p-value = 0.0005) and in female (rho = 0.58, adjusted p-value = 0.004) patients. In conclusion, gonadotroph tumors exhibit histological characteristics pinpointing the existence of several subtypes. Their heterogeneity warrants further investigations and may have to be taken into account when studying these tumors and investigating treatment options.

Intratumoural spatial distribution of S100B + folliculostellate cells is associated with proliferation and expression of FSH and ERα in gonadotroph tumours

“…A similar correlation was also found between the percentage of FSH + cells and ERα + cells, suggesting the occurrence of tumour areas simultaneously rich and poor in FSH + , ERα + , and S100B + cells. Consistently, a positive correlation between FSH and ERα at the whole tumour level has already been reported in gonadotroph tumours [ 30 , 36 ], suggesting that our technical approach is appropriate to investigate spatial associations of marker co-expression. Given the fact that ERα is also expressed in the vast majority of normal human gonadotroph cells which produce, secrete and stain for FSH [ 37 , 38 ], we hypothesize that gonadotroph tumour cells expressing ERα and FSH might be closer to a normal phenotypic state than gonadotroph tumour cells lacking ERα and FSH expression.…”

“…The identification of a heterogeneous spatial distribution of S100B + cells in individual gonadotroph tumours led us to question whether the spatial distribution of S100B + cells may be of functional relevance in these tumours. To address this question, we built a cartography based on the IHC analysis of multiple markers on serial tumour sections, including five new markers, namely Ki67 (a proliferation marker), FSH and LH (the two hormones produced by gonadotroph cells), SSTR2 (a potential marker of response to treatment), and ERα (a transcription factor and a potential marker of response to treatment) [ 26 , 30 ] (Fig. 5 A).…”

“…The concepts of intratumoural, intertumoural and interpatient heterogeneity are intensively studied and acknowledged to be of tremendous importance in cancer biology [ 31 , 32 ]. In PitNETs, tumour heterogeneity has only started to be unravelled by recent studies [ 30 , 33 , 34 ]. Here, our work contributes to extending this knowledge by providing an insight into the heterogeneity of PitNETs through the cartography of a rare TME component, namely S100B-expressing FS cells.…”

Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer

“…The scoring method of positive tumor cell percentage was as follows: zero points: no positive tumor cell, one point: percentage of positive tumor cells is <10%, two points: percentage of positive tumor cells is 10–50%, three points: percentage of positive tumor cells is 50–80%, and four points: percentage of positive tumor cells is >80%. Finally, the above two scores were multiplied to obtain the immunoreactive score (IRS) [ 14 ]. For VEGF, IRS greater or equal to 4 were considered to indicate high expression, whereas scores lower than 4 were considered to indicate low expression.…”

Correlation between quantitative perfusion histogram parameters of DCE-MRI and PTEN, P-Akt and m-TOR in different pathological types of lung cancer

“…After dehydration, transparency and mounting, the slides were visualized using a microscope. The immunostaining results of specific antibodies were measured semi-quantitatively by immunoreactive score (IRS) method [ 13 ]. The specific calculation method of IRS is as follows: Staining intensity (SI) classification: 0, no staining; 1, light yellow; 2, brown yellow, 3, dark brown; percentage of stained cells (PP): 0, no staining; 1, staining in < 10% of tumor cells; 2, staining in 10–50% of cells; 3, staining in 50–80% of cells; 4, staining in > 80% of cells.…”