scholarly journals MON-269 FGFR-4 Expression in Pituitary Adenomas Is Associated with Aggressive Tumor Features

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pinar Kadioglu ◽  
Emre Durcan ◽  
Fatma Ela Keskin ◽  
Hande Mefkure Ozkaya ◽  
Sabri Sirolu ◽  
...  
Keyword(s):  
Cavernous Sinus ◽  
Pituitary Adenomas ◽  
Pituitary Surgery ◽  
Pathological Examination ◽  
Clinical Parameters ◽  
Ki 67 ◽  
Cavernous Sinus Invasion ◽  
Significant Difference ◽  
Aggressive Tumor ◽  
The Mean

Abstract Biomarkers predicting tumor aggressiveness in pituitary adenomas have been largely investigated, albeit, with inconsistent results. We investigated the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression and determined its relationship with radiological, pathological, and clinical parameters. In our study, 650 patients who were followed up for pituitary disease were reviewed from medical charts retrospectively. Of the 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we selected 161 cases on the basis of availability of pathology specimen of hypophysis tissue in our center. Patients’ radiological, pathological, and clinical parameters were obtained from medical charts. FGFR-4 immunostaining was evaluated using a semiquantitative Histologic score (H score). The mean age of the patients was 56.02 ± 14.80 years. Ninety-two (57.1%) were male and 69 (42.9%) were female. The mean follow-up period was 68.94 ± 44.15 months. Pathological examination revealed the following subtypes; 53 nonfunctioning pituitary adenomas, 26 corticotroph adenomas, 25 hormone receptor negative adenomas, 22 mammotroph adenomas, 13 somatotroph adenomas, 8 combined hormone secreting adenomas, 7 somatomammotroph, and 7 PIT-1 positive adenomas. The mean tumor size was 26.83 ± 14.92 mm. In patients with cavernous sinus invasion, the mean adenoma size was significantly higher than those without (p <0.001). Mean H-score and Ki-67 levels were not different between patients with and without cavernous sinus invasion (p>0.05 for all). The mean H-score, Ki-67, and adenoma size were significantly higher in patients without remission than those with remission (p <0.001, p = 0.014, p <0.001, respectively). The mean H score and adenoma size were significantly higher in patients with residual lesions than those without (p = 0.002, p <0.001; respectively); there was no significant difference in Ki- 67 levels (p>0.05). When the H-score and Ki-67 levels were assessed in terms of gender, sellar-dural invasion, tumor function or presence of poor subtype, no significant difference was detected (p>0.05 for all). The mean H score and adenoma size were significantly higher in patients with Ki-67≥ 3 than those with <3 (p = 0.002, p = 0.004; respectively). There was a weak positive correlation between H-score and Ki-67 (p = 0.005; r = 0.218); on the other hand, Ki-67 was not correlated with mitosis grade, p53 staining, and age, respectively (p>0.05 for all). In our study, we demonstrated that patients with residual lesion and those without remission had high expression of FGFR-4. Also FGFR-4 levels were positively correlated with Ki-67 which itself correlated with lack of remission. Taken together, our results indicate that higher levels of FGFR-4 and Ki-67 in pituitary adenomas might indicate a more aggressive tumor phenotype.

Fibroblast Growth Factor Receptor-4 Expression in Pituitary Adenomas is Associated with Aggressive Tumor Features

2021 ◽  
Author(s):  
Emre Durcan ◽  
Fatma Ela Keskin ◽  
Hande Mefkure Ozkaya ◽  
Sabri Sirolu ◽  
Serdar Sahin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Pituitary Adenomas ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Clinical Parameters ◽  
Fibroblast Growth ◽  
Ki 67 ◽  
Aggressive Tumor ◽  
The Mean

Abstract Purpose To investigate the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression with radiologic, pathologic, and clinical parameters in pituitary adenomas. Methods Among 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we included 161 patients (53 gonadotroph, 26 corticotroph, 25 null cell, 22 lactotroph, 13 somatotroph, 8 adenomas with unusual combination, 7 Pit-1 positive adenomas, and 7 lactosomatotroph) based on availability of pathology specimens. Patients’ radiologic, pathologic, and clinical parameters were determined. FGFR-4 immunostaining was evaluated using a semi-quantitative histologic score (H-score). Results The mean follow-up period was 61 (IQR=32–84) months. The median H-scores for FGFR-4 were higher in patients without remission, those with residual lesion, and T2-hyperintense adenoma (p<0.05). Ki-67 level was higher in patients without remission compared to those in remission (p<0.05). The mean Ki-67 levels did not differ between patients with and without residual lesion or T2-hyperintense tumor (p>0.05). There was no significant difference (p>0.05) when the H-score and Ki-67 levels were assessed in terms of sex, sellar-dural invasion, Knosp and a grading system for superior, inferior, parasellar, anterior and posterior tumor extension Classification, tumor function or presence of poor subtype. Adenomas with Ki-67 expression ≥3% had higher FGFR4 expression levels than those with <3% expression (p=0.002). There was a weak positive correlation between H-score and Ki-67 (p=0.011; r=0.201). Conclusions Higher levels of FGFR-4 in pituitary adenomas could be use a marker for more aggressive tumor behavior.

The Past, Present, and Future Statuses of Formerly Classified “Atypical Pituitary Adenomas”: A Clinicopathological Assessment of 101 Cases in a Cohort of More than 1,000 Pure Endoscopically Treated Patients in Single Center

2020 ◽  
Author(s):  
Ercan Bal ◽  
İbrahim Kulaç ◽  
Selim Ayhan ◽  
Figen Söylemezoğlu ◽  
Mustafa Berker
Keyword(s):  
Pituitary Adenomas ◽  
Labeling Index ◽  
World Health ◽  
Pituitary Neoplasms ◽  
Ki 67 ◽  
Cavernous Sinus Invasion ◽  
Atypical Adenoma ◽  
Endocrine Organs ◽  
Significant Difference ◽  
Cure Rates

Abstract Aim This study was aimed to assess the clinical aggressiveness of pituitary neoplasms that were previously defined as atypical adenomas. Methods A total of 1,042 pituitary adenomas were included in the study and 101 of them were diagnosed as atypical adenoma. Demographic characteristics, radiological evaluations, and clinical information were obtained from a computer-based patient database. Cases were categorized as atypical or typical using the criteria listed in 2004 Classification of Tumors of Endocrine Organs. Results The cure and reoperation rates did not show any statistically significant difference between the typical and atypical adenomas. However, a higher Ki-67 labeling index was found to be associated with a higher rate of reoperation (p = 0.008) in atypical adenomas. Of note, cavernous sinus invasion or parasellar extension was found to be associated with lower cure rates in patients with atypical pituitary adenomas (p < 0.001 and p = 0.001, respectively). Conclusion Although atypical pituitary adenomas are known to be more invasive, this study demonstrated that the reoperation and cure rates are the same for typical and atypical adenomas. Our findings advocate for omitting the use of atypical adenoma terminology based solely on pathological evaluation. As stated in the 4th edition of the World Health Organization (WHO) classification, accurate tumor subtyping, evaluation of proliferation by means of mitotic count and Ki-67 labeling index, and radiological and intraoperative assessments of tumor invasion should be taken into consideration in the management of such neoplasms.

scholarly journals Immunohistochemical Analyses of Cell Cycle-related Proteins, Apoptosis, and Proliferation in Pituitary Adenomas

2001 ◽  
Vol 49 (9) ◽  
pp. 1193-1194 ◽  
Author(s):  
Hiromichi Nakabayashi ◽  
Ichiro Sunada ◽  
Mitsuhiro Hara
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Cyclin A ◽  
Proliferative Potential ◽  
Ki 67 ◽  
Recurrent Group ◽  
Significant Difference ◽  
The Mean ◽  
Related Proteins

To analyze the cell cycle regulatory mechanisms in the growth of pituitary adenomas, we investigated immunohistochemically the expression of the cell cycle-related proteins cyclin A and p27 in 48 pituitary adenomas. The frequency of apoptosis and the proliferative potential were also examined. The percentage of apoptotic cells was evaluated by immunohistochemical analysis using the anti-single-strand DNA antibody. The proliferative potential was assessed using the anti-Ki-67 antibody. The mean cyclin A labeling index (LI) for the non-recurrent group was 1.03% and for the recurrent group 2.31%. A positive linear correlation between cyclin A LI and Ki-67 LI was found. The mean p27 LI for the non-recurrent group was 67.4% and for the recurrent group 47.0%. There were significant differences in cyclin A LI and p27 LI between the non-recurrent group and the recurrent group. The mean apoptotic rate for the non-recurrent group was 0.87% and for the recurrent group 1.05%. There was no significant difference. Multivariate regression analysis revealed that high cyclin A LI and high Ki-67 LI were significant factors for shorter progression-free survival. The results suggest that the cyclin A LI is a useful prognostic factor in pituitary adenomas. (J Histochem Cytochem 49:1193–1194, 2001)

Coexistence of intracranial aneurysm in 800 patients with surgically confirmed pituitary adenoma

2012 ◽  
Vol 116 (5) ◽  
pp. 942-947 ◽  
Author(s):  
Min Chul Oh ◽  
Eui Hyun Kim ◽  
Sun Ho Kim
Keyword(s):  
Pituitary Adenoma ◽  
Intracranial Aneurysm ◽  
Cavernous Sinus ◽  
Patient Population ◽  
Pathological Examination ◽  
Control Group ◽  
Cavernous Sinus Invasion ◽  
Factors Associated ◽  
Significant Difference ◽  
Matched Comparison

Object The purpose of this study was to assess factors associated with intracranial aneurysm (IA) in patients with pituitary adenoma (PA). In addition, these patients were compared with a control group from the general patient population in terms of the age-matched prevalence rate and the pattern of distribution of IA. Methods The authors retrospectively reviewed 800 patients who received transsphenoidal surgery for PA and 3850 control patients from the general patient population who were evaluated for routine health care at the authors' institution between 2004 and 2010. All patients underwent MR imaging and MR angiography. Hormone assessment and pathological examination performed using immunohistochemical (IHC) staining were completed for patients with PA. Results Coexistence of IA in patients with PA was detected in 18 patients (2.3%). Multivariate analysis showed that age (p = 0.04) and cavernous sinus invasion (p < 0.001) were correlated with the increased incidence of IA, but hormone type, IHC staining, and sex were not associated. An age-matched comparison of the prevalence of IA showed an increased prevalence in patients with PA compared with the controls (p = 0.014), and when categorized according to age by decade, the 6th decade was significantly different (p = 0.039). However, the intracranial distribution pattern of IA did not demonstrate a significant difference. Conclusions Older age and the existence of a cavernous sinus invasion were correlated with increased incidence of IA in patients with PA. An age-matched comparison showed an increased incidence of IA in patients with PA than in the controls.

Atypical pituitary adenoma: a clinicopathologic case series

2018 ◽  
Vol 128 (4) ◽  
pp. 1058-1065 ◽  
Author(s):  
Martin J. Rutkowski ◽  
Ryan M. Alward ◽  
Rebecca Chen ◽  
Jeffrey Wagner ◽  
Arman Jahangiri ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Mitotic Activity ◽  
Cavernous Sinus ◽  
Pituitary Adenomas ◽  
Cavernous Sinus Invasion ◽  
Female Patients ◽  
Mean Diameter ◽  
Atypical Pituitary Adenoma ◽  
Male Patients ◽  
The Mean

OBJECTIVEIn 2004, the WHO classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. The authors sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma.METHODSThe authors reviewed records of patients who underwent resection of pituitary adenoma at the University of California, San Francisco, between 2007 and 2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB-1 index ≥ 3%). Statistical analyses were performed using χ2, Fisher’s exact test, t-test, log-rank, and logistic regression.RESULTSBetween 2007 and 2014, 701 patients underwent resection for pituitary adenoma. Among these patients, 122 adenomas exhibited mitotic activity and therefore were evaluated for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the nonatypical cohort (p = 0.231). The mean age of patients in the atypical cohort was 37 years (range 10–65 years), which was significantly lower than the mean age of 49 years (range 10–93 years) for patients in the nonatypical cohort (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas were more likely to be functional (78%) than nonatypical adenomas (42%; p < 0.001). Functional atypical adenomas were significantly larger than functional nonatypical adenomas (mean diameter 2.2 vs 1.4 cm; p = 0.009), as were nonfunctional atypical adenomas compared with nonfunctional nonatypical adenomas (mean diameter 3.3 vs 2.3 cm; p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001), and subtotal resection was associated with cavernous sinus invasion (p < 0.001) and larger size (p < 0.001) on binomial multivariate regression. The median time until recurrence was 56 months for atypical adenomas, 129 months for functional nonatypical adenomas, and 204 months for nonfunctional nonatypical adenomas (p < 0.001). Functional atypical adenomas recurred more frequently and significantly earlier than functional nonatypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, sex, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002).CONCLUSIONSWhen compared with nonatypical pituitary adenomas, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecretory, and are associated with earlier recurrence. These features lend credence to atypical pituitary adenomas being a distinct clinical entity in addition to a discrete pathological diagnosis.

Endoscopic Endonasal Management of Nonfunctioning Pituitary Adenomas with Cavernous Sinus Invasion: Our Experience

2013 ◽  
Vol 149 (2_suppl) ◽  
pp. P48-P48
Author(s):  
Fabio Ferreli ◽  
Mario Turri-Zanoni ◽  
Stefania Gallo ◽  
Maurizio Bignami ◽  
Giustino Tomei ◽  
...  
Keyword(s):  
Cavernous Sinus ◽  
Pituitary Adenomas ◽  
Endoscopic Endonasal ◽  
Cavernous Sinus Invasion ◽  
Nonfunctioning Pituitary Adenomas

scholarly journals Association of different pathologic subtypes of growth hormone producing pituitary adenoma and remission in acromegaly patients: a retrospective cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Dehghani ◽  
Zahra Davoodi ◽  
Farahnaz Bidari ◽  
Amin Momeni Moghaddam ◽  
Davood Khalili ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cohort Study ◽  
Cavernous Sinus ◽  
Retrospective Cohort Study ◽  
Pituitary Adenomas ◽  
Retrospective Cohort ◽  
Remission Rate ◽  
Cavernous Sinus Invasion ◽  
Dual Staining

Abstract Background Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients. Methods A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models. Results Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01–0.67; p = 0.015) and 64% (95% CI: 0.19–0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups. Conclusion Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission.

scholarly journals Safety and efficacy of mini doppler in recurrent pituitary tumours

2020 ◽  
pp. 336-342
Author(s):  
Moshiur Rahman ◽  
Ezequiel Garcia-Ballestas ◽  
Luis Rafael Moscote-Salazar
Keyword(s):  
Cavernous Sinus ◽  
Surgical Excision ◽  
Pituitary Surgery ◽  
Pituitary Tumour ◽  
Csf Leak ◽  
Surgical Removal ◽  
Pituitary Tumours ◽  
Female Ratio ◽  
Cavernous Sinus Invasion ◽  
Number Of Patients

Background: Pituitary surgery is the most common surgery used to remove pituitary tumours. The use of mini doppler in surgical removal of an endonasal pituitary tumour has shown good short-term clinical outcomes and few complications in patients. Cavernous sinus invasion limits the surgical excision and still a challenge of gross total resection.   Objective: The main objective of this study is to evaluate the outcome of surgical removal of an endonasal pituitary tumour using mini doppler.    Method: A total of 12 patients were studied retrospectively from 2012 to 2018 in a single institution (Private hospital) in Dhaka, Bangladesh. The male and female ratio was 7:5. Results: 92% of cases of the total number of patients had satisfactory removal/ neurological improvement/hormonal improvement. Among 12 cases, 8 cases had transient diabetes insipidus and one patient had CSF leak.    Conclusion: The intraoperative Doppler is a useful tool to localize the carotids, which provides safer resection of endonasal pituitary tumours. Thus, it is very safe and effective for laterosellar resection of recurrent pituitary tumours and for cavernous sinus invasions.

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