Metastatic prolactinoma: case report with immunohistochemical assessment for p53 and Ki-67 antigens

Abstract

-Pituitary carcinomas are rare neoplasms characterized by craniospinal and/or systemic metastases originated from the pituitary. Their histopathology is frequently indistinguishable from that of benign adenomas. The development of markers that better reflect their behavior is desirable. We present the case of a 47 year-old man with a pro l a c t i n -s e c reting macroadenoma who was submitted to surgeries, cranial radiation therapy, and bromocriptine treatment, but evolved to a fatal outcome after the disclosure of int r a c r anial metastases. Tumor samples underwent p53 and Ki-67 immunohistochemical assessment. p53 was absent in all samples, a rare finding among pituitary carcinomas. Ki-67 proliferative index was 2.80% in the original tumor, 4.40% in the relapse, and 4.45% in the metastasis. The figure in the relapse is higher than the expected for a noninvasive adenoma. In conclusion, p53 staining is not positive in all pituitary carc i n o m a s . A high Ki-67 proliferative index in a pituitary adenoma might indicate a more aggressive behavior.KEY WORDS: prolactinoma, pituitary carcinoma, metastasis, p53, Ki-67. P rolactinoma metastático: relato de caso com avaliação imuno-histoquímica para os antígenos p53 e Ki-67 RESUMO -Carcinomas pituitários são neoplasias raras caracterizadas pela presença de metástases cranioespinhais e/ou sistêmicas originadas da hipófise. Sua histopatologia é freqüentemente indistinguível daquela dos adenomas benignos. O desenvolvimento de marc a d o res que melhor reflitam o seu comport a m e nto é desejável. Apresentamos o caso de um homem de 47 anos com um macroadenoma secretor de pro l a c t i n a que foi submetido a procedimentos cirúrgicos, radioterapia e tratamento com bromocriptina, mas que e v o l u i u para o óbito após o descobrimento de metástases intracranianas. Amostras do tumor foram submetidas à a n á-lise imuno-histoquímica para os antígenos p53 e Ki-67. A coloração para p53 foi negativa em todas as amostras, um achado raro entre os carcinomas pituitários. O índice proliferativo Ki-67 foi 2,80% no tumor origin a l , 4,40% na recidiva e 4,45% na metástase. O valor obtido na recidiva é maior que o esperado para um adenoma não-invasor. Concluindo, a coloração para p53 não é positiva em todos os carcinomas pituitários. Um í n d i c e proliferativo Ki-67 alto em um adenoma pituitário poderia indicar um comportamento mais agressivo. PALAVRAS-CHAVE: prolactinoma, carcinoma pituitário, metástase, p53, Ki-67.The prevalence of clinically overt pituitary tumors is around 0.02% of the population

Pituitary Carcinomas

“…It may be nevertheless considered aggressive a pituitary adenomas when there is a change in the behavior of a previous adenoma. Some authors [4,19] suggest that primary tumors with mitotic activity, as with increased (>3%) MIB-1 labeling index, and/or p53 immunoreactivity, should be defined as 'aggressive adenomas' to denote their aggressive potential and indicating a possibility for future malignant transformation [6].…”

“…Approximately 140 cases of pituitary carcinoma were reported in an extensive review of the British literature up to 2005 [6], and additional 10 cases have been reported afterwards [1,2,[4][5][6][7][8][12][13][14][15][16][17][18][19][20][21] (table 1). Pituitary carcinomas have no gender difference and are diagnosed at a mean age of 44 years, with a latency period of 7 years after the initial diagnosis of a pituitary tumor [1,6].…”

Identification of genes differentially expressed between benign and osteopontin transformed rat mammary epithelial cells

“…Eighteen % and 38% cDNAs were differentially expressed by over 15-fold in the benign and malignant breast tumor cell lines, respectively. Amongst the cDNAs expressed at a higher level in the R37-OPN cells than in the R37 cells were previously characterized breast cancer-associated genes such as TPTI [ 14 ], ARNT [ 15 ], CSFIR [ 16 ], MDM2 [ 17 ], CD44 [ 18 ], Cxcr4 [ 19 ], RAN GTPase [ 20 ], cytokeratin 20 (CK20) [ 21 ], Ki67 [ 22 ], with fold increases of 8, 8, 9, 9, 11, 23, 25, 32, and 45, respectively. Amongst the cDNAs expressed at a lower level in R37-OPN cells were previously characterized cancer suppressor genes PTEN [ 23 ], ATM [ 24 ] and BRCA1 associated protein 1 [ 24 ] with decreases of 19, 23 and 23 fold, respectively.…”

PTTG and Ki-67 expression in pituitary adenomas

“…Pituitary tumours, in majority of cases benign adenomas, account for 10-25% of intracranial tumours, their prevalence in the general population being 0. 02% [1,2], Anatomically, these tumours are classified as microadenomas (diameter<1cm) or ma croadenomas (diameter 21 cm) [1,3].…”

“…Clinically, pituitary tumours may be accompanied by hormonal activity or symp toms of "mass effect", such as invasion of the surrounding tissues (e. g. supra-sellar extension, sinus cavernous invasion and optic nerve compression), causing visual disturbances or headache. Compression of non-tumour pituitary results in varying degrees of hypopituitarism [2], Based on physical examination and blood hormone levels, pituitary tumours can be broadly classified as either functioning (FPA) or non-functioning pituitary adenomas (NFPA) -comprising approximately 30% of all ade nomas [1]. In about 10% of autopsies small pituitary adenomas are found, most of them having had no clinical manifestation [3].…”