Sample Characteristics
The patient cohort included 38 cases, aged 12–20 years (17.67 ± 1.63 years), of which 23 were males and 15 were females, accounting for 3.5% of the 1073 surgically treated pituitary patients in the same period. The clinical manifestations are: headache, menstrual disorder, visual impairment, accelerated development, galactorrhea, growth retardation, gynaecomastia, etc. (Table 1). Of these, 13 were invasive PA cases and 12 were cases of apoplexy (31.58%). The texture of the tumor was soft in 30 cases (78.95%), moderate in three cases (7.89%), and tough in five cases (13.16%).
Table 1
Summary of the clinical characteristics of 38 patients
Characteristics | number | % |
Age | | |
Mean | 17.67 ± 1.63 | / |
Group | | |
12–14 | 5 | 13.16 |
15–20 | 33 | 86.84 |
Gender | | |
Female | 15 | 39.47 |
Male | 23 | 60.53 |
Presenting symptom | | |
Headache | 17 | 44.74 |
Menstrual disorders | 12 | 31.58 |
Visual impairment | 11 | 28.95 |
Accelerated development | 4 | 10.53 |
Galactorrhea | 4 | 10.53 |
Growth retardation | 3 | 7.89 |
Gynaecomastia | 2 | 5.26 |
Max tumor dimension | | |
Microadenoma | 4 | 10.53 |
Macroadenoma | 15 | 39.47 |
Giant adenoma | 19 | 50.00 |
Extent of adenoma | | |
Purely intrasellar | 9 | 23.68 |
Suprasellar extension | 18 | 47.37 |
Cavernous sinus invasion | 8 | 21.05 |
Third ventricle invasion | 2 | 5.26 |
Anterior cranial fossa extension | 1 | 2.63 |
Immunohistochemical Analysis
Of the 38 specimens, 15 were negative for MGMT expression, one was positive for expression less than 10%, three were positive for 25–50%, and 19 were showed an expression greater than 50%. Therefore, 16 specimens (42.11%) displayed a low expression of MGMT. Ki-67 expression ranged between 1% and 10% (mean 4.24 ± 2.71%). Considering a Ki-67 expression greater than 3% as the diagnostic criteria of the original atypical pituitary adenoma, the tumors were divided into low and high expression groups. Low MGMT expression was observed in 5/18 (27.78%) and 11/20 (55.00%) specimens in the Ki-67 high and low expression groups, respectively. Alternately, low MGMT expression was observed in 5/12 (41.67%) and 6/13 (46.15%) specimens in the apoplexy and the invasive group, respectively. In the recurrent group, 2/6 (33.33%) specimens showed low MGMT expression. p53 positive tumors were found in 22/38 (57.89%) patients.
MGMT Expression Instability
Two patients in this cohort were treated with two surgeries each in our center,and MGMT protein expression was detected in the specimens. In these two patients, one of them was a 12-year-old boy with growth hormone pituitary adenoma. The first transsphenoidal surgery failed to completely remove the tumor, so the tumor recurred 11 months after the surgery, and the tumor was finally completely removed by pterional approach. However, MGMT expression was 95% (high expression), Ki-67 was 4% and p53 was negative in the sample in first operation (Fig. 1C) and 10% (low expression), Ki-67 was 2% and p53 also was negative in the second sample in the second surgery (Fig. 1F). In the other patient with nonfunctioning pituitary adenoma, after the first transsphenoidal subtotal resection of pituitary adenoma, the second transsphenoidal resection was performed 10 months later due to tumor recurrence. The first specimen was negative and the second specimen was 60% positive for MGMT (high expression). Ki-67 and p53 were expressed relatively stably (Fig. 1A, B, D, and E).
MGMT and Tumor Biological and Molecular Characterization
The Chi-square test or logistic regression were used to analyze the relationship between the expression of MGMT and age, gender, tumor biological characteristics such as diameter, invasiveness, texture, apoplexy, Ki-67, and p53 expression. A significant correlation was identified between the tumor diameter and MGMT expression (B = 2.56, SE = 0.99, P = 0.01, Exp (B) = 12.89). The larger the tumor diameter, the higher the MGMT expression. The remaining indicators did not show a correlation (Table 2).
Table 2
Correlation of MGMT expression with clinical and biological characteristics.
Variables | | MGMT immuno-expression | |
| low expression | high expression | p value |
Age (mean ± SD) (years) | 17.50 ± 1.79 | 16.77 ± 2.56 | |
Maximum diameter (mean ± SD) (mm) | 24.88 ± 14.32 | 29.64 ± 15.16 | |
Age group (years) | | | 0.37 |
12–14 | 1 | 4 | |
15–20 | 15 | 18 | |
Gender | | | 0.92 |
Male | 9 | 12 | |
Female | 7 | 10 | |
Diameter(mm) | | | 0.01 |
༜10 mm | 4 | 0 | |
10–40 mm | 10 | 15 | |
༞40 mm | 2 | 7 | |
Invasiveness | | | 0.72 |
Yes | 6 | 7 | |
No | 10 | 15 | |
Type | | | 0.09 |
Slient adenoma | 3 | 3 | |
Lactotroph adenomas | 11 | 10 | |
Corticotroph adenomas | 0 | 1 | |
Somatotroph adenomas | 1 | 8 | |
Plurihormonal adenomas | 1 | 0 | |
Texture | | | 0.48 |
Soft | 14 | 16 | |
Medium | 1 | 2 | |
Tough | 1 | 4 | |
P53 | | | 0.58 |
Positive | 8 | 13 | |
Negative | 8 | 9 | |
Ki-67 | | | 0.09 |
༞3% | 5 | 13 | |
≤3% | 11 | 9 | |
Apoplexy | | | 0.97 |
Yes | 5 | 7 | |
No | 11 | 15 | |
Recurrence | | | 0.98 |
Yes | 2 | 4 | |
No | 14 | 18 | |
MGMT and Prognosis
The cohort was followed up from 3 months to 65 months (mean 34.84 ± 20.81 months). Among them, eight cases relapsed and the recurrence time ranged from 10 months to 52 months (mean 25.25 ± 17.09 months). Among the recurrence cases, four showed low MGMT expression (50.00%). In the non-relapsed cases, 12/30 (40.00%) showed a low MGMT expression. Statistical analysis did not show a correlation between tumor recurrence and MGMT expression (p = 0.87).