Prolaktinomalı hastalarda siklin D1 Gen (CCND1) polimorfizminin tümör davranışı üzerine etkisi ve tümör invazifliğini etkileyen klinik ve patolojik özellikler
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Date
2011
Authors
Cander, Soner
Journal Title
Journal ISSN
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Publisher
Uludağ Üniversitesi
Abstract
Prolaktinomalar çoğunlukla benign seyirli olmakla beraber tümör boyutu, invazifliği ve tedaviye yanıt açısından farklılıklar gösterebilmektedir. Bu çalışmada prolaktinomalı olgularda siklin D1 gen polimorfizminin tümör davranış özellikleri üzerine etkisinin incelenmesi ve laktotrof adenomun radyolojik ve patolojik özelliklerinin medikal ve cerrahi tedaviye yanıtı üzerine etkisinin değerlendirilmesi amaçlanmıştır.Çalışmaya prolaktinoma tanısı ile takip edilen 113 hasta dahil edildi. Tüm hastalardan periferik kan örneklemesi ile siklin D1 genindeki A870G polimorfizmi belirlenerek genotipleme yapıldı. Radyolojik bulgularına göre invazif/noninvazif, mikro/makro/dev adenom guruplarına ve opere olan hastalar histopatolojik incelemede Ki67 indeksi oranına göre sınıflandırıldı. Guruplar arasında siklin D1 gen polimorfizmi karşılaştırıldı. Ayrıca hastaların tanı yaşı, cinsiyeti, tümör boyutu ve serum prolaktin seviyesinin tümör agresivitesi ile ilişkisi araştırıldı.Çalışmaya alınan 113 hastanın erkek/kadın oranı 27/86 ve tanı yaşı ortalamaları 34.4 yıl (Erkeklerde 40.3, kadınlarda 32.6) idi. 68 hasta (%60.2) noninvazif, 45 hasta (%39.8) invazif gurupta yer aldı. 15 (%13.3) hastada GG, 58 (%51.3) hastada GA ve 40 (%35.4) hastada AA genotipi tespit edildi. Noninvazif ve invazif gurupta A allel sıklığı %60.3 ve %62.2 idi. İnvazif ve noninvazif gurupların genotip dağılımları ve allel sıklıklarında anlamlı farklılık tesbit edilmedi. Erkek hastalarda tümör boyutu, makroadenom ve invazif adenom oranı anlamlı olarak yüksek bulundu. Ki67 indeksi ile invazif/noninvazif guruplar arasında anlamlı bir ilişki saptanmadı. Prolaktin seviyeleri ve tümör boyutu arasında pozitif korelasyon saptandı. İnvazif gurupta tümör çapında ve prolaktin seviyesinde azalma oranları anlamlı olarak yüksek bulundu.Siklin D1 A870G polimorfizminin prolaktinomalarda tümör davranışı üzerinde önemli rol oynamamaktadır. İnvazif adenomlarda tedavi yanıtı noninvaziflerden daha kötü değildir. Tümör invazifliği prolaktinomalarda prognozu olumsuz etkilememektedir.
Although most prolactinomas are benign, they may show differences in tumor size, invasiveness and treatment response. In this study, we aimed to evaluate the effect of cyclin D1 gene polymorphism on attribute of tumor behaviour and to investigate the effects of radiological and pathological features of adenoma on the response to medical and surgical treatment in prolactinomas.One hundred and thirteen patients followed with the diagnosis of prolactinoma were included the study. The cyclin D1 gene A870G polymorphism was determined in all patients with peripheral blood sampling. Patients were classified into invasive / non-invasive and micro / macro / giant adenoma groups according to the radiological findings and categorized according to their Ki67 index. Cyclin D1 gene polynorphism was compared between each group. Age at diagnosis, gender, tumor size, serum prolactin levels were evaluated in the relation to the tumor aggressiveness.In total of 113 patients, male / female ratio was 27/86 and the mean age at diagnosis was 34.4 year (men 40.3, women 32.6). Sixty-eight patients (60.2%) took place in non-invasive group while 45 patients (39.8%) were in invasive group. GG, GA and AA genotype were found in 15 (13.3%), 58 (51.3%) and 40 (35.4%) of patients respectively. A allele frequency was 60.3% in noninvasive and 62.2% in invasive groups. Genotype distributions and allele frequencies in invasive and noninvasive groups were not significantly different. In male patients, tumor size, rate of macroadenomas and invasive adenomas were significantly higher. There was not a significant relationship between Ki 67 index and invasive / noninvasive groups. There was a positive correlation between prolactin levels and tumor size. Reduction in tumor size and serum prolactin levels were significantly higher in invasive group.Cyclin D1 A870G polymorphism does not play an important role in tumor behavior in prolactinomas. Treatment response in invasive adenomas is not bad than noninvasive adenomas. Tumor invasiveness is not an important factor on the prognosis of prolactinomas.
Although most prolactinomas are benign, they may show differences in tumor size, invasiveness and treatment response. In this study, we aimed to evaluate the effect of cyclin D1 gene polymorphism on attribute of tumor behaviour and to investigate the effects of radiological and pathological features of adenoma on the response to medical and surgical treatment in prolactinomas.One hundred and thirteen patients followed with the diagnosis of prolactinoma were included the study. The cyclin D1 gene A870G polymorphism was determined in all patients with peripheral blood sampling. Patients were classified into invasive / non-invasive and micro / macro / giant adenoma groups according to the radiological findings and categorized according to their Ki67 index. Cyclin D1 gene polynorphism was compared between each group. Age at diagnosis, gender, tumor size, serum prolactin levels were evaluated in the relation to the tumor aggressiveness.In total of 113 patients, male / female ratio was 27/86 and the mean age at diagnosis was 34.4 year (men 40.3, women 32.6). Sixty-eight patients (60.2%) took place in non-invasive group while 45 patients (39.8%) were in invasive group. GG, GA and AA genotype were found in 15 (13.3%), 58 (51.3%) and 40 (35.4%) of patients respectively. A allele frequency was 60.3% in noninvasive and 62.2% in invasive groups. Genotype distributions and allele frequencies in invasive and noninvasive groups were not significantly different. In male patients, tumor size, rate of macroadenomas and invasive adenomas were significantly higher. There was not a significant relationship between Ki 67 index and invasive / noninvasive groups. There was a positive correlation between prolactin levels and tumor size. Reduction in tumor size and serum prolactin levels were significantly higher in invasive group.Cyclin D1 A870G polymorphism does not play an important role in tumor behavior in prolactinomas. Treatment response in invasive adenomas is not bad than noninvasive adenomas. Tumor invasiveness is not an important factor on the prognosis of prolactinomas.
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Keywords
Prolaktinoma, Tümör invazifliği, Siklin D1 gen polimorfizmi, Tümör boyutu, Ki67 indeksi, Prolactinoma, Tumor invasiveness, Cyclin D1 gene polymorphism, Tumor size, Ki 67 index
Citation
Cander, S. (2011). Prolaktinomalı hastalarda siklin D1 Gen (CCND1) polimorfizminin tümör davranışı üzerine etkisi ve tümör invazifliğini etkileyen klinik ve patolojik özellikler. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.