Prognostic Value of Cyclin D1 Overexpression in Invasive Breast Carcinoma

Abstract

Objective: Breast cancer is the most diagnosed cancer worldwide, accounting for 11.7% of all cancers. Cyclin D1, a regulator of CDK4/6 and cell cycle progression, functions as an oncogene through overexpression, contributing to the pathogenesis of cancers including breast carcinoma. This study aimed to evaluate Cyclin D1 expression and its clinicopathological significance in invasive breast carcinoma within the Turkish population. Methods: H&E-stained and immunohistochemical preparations from partial and total mastectomy specimens of 143 patients, diagnosed between 2007 and 2013, were examined. Cyclin D1 overexpression was evaluated in 1000 cells using an IHC score based on nuclear staining intensity (0-3) and the percentage of positive tumor cells (1-3), classified as weak ('+' or '++') or strong positive ('+++'). Pearson's Chi-Square and Spearman's rho were used to analyze the relationship between Cyclin D1 expression and clinicopathological parameters statistically. Results: The median age of the patients was 58.5 years (Min:28, Max:92). Cyclin D1 status showed no correlation with age, T stage, or lymph node metastasis. However, a moderate positive correlation was observed with ER (r = 0.32, P <.001) and PR (r = 0.31, P <.001) scores. Among molecular subgroups, Cyclin D1 overexpression was most significant in Luminal B group (92.9%, P = .008), while Triple-negative group showed significantly lower overexpression (40%, P = .008). Conclusion: Cyclin D1 overexpression in Luminal B and Luminal A groups, along with its positive correlation with ER, suggests its role in estrogen-sensitive breast cancer pathogenesis. Strong Cyclin D1 overexpression was associated with reduced survival time in HER2-positive cases.

Keywords

• Breast
• invasive breast carcinoma
• Cyclin D1
• histopathology
• immunohistochemistry

İnvaziv Meme Karsinomunda Cyclin D1 Aşırı Ekspresyonunun Prognostik Değeri

Abstract

Amaç: Meme kanseri, dünya genelinde en sık tanı konulan kanser olup tüm kanserlerin %11,7’sini oluşturmaktadır. Cyclin D1, CDK4/6 ve hücre döngüsü ilerlemesini düzenleyen bir onkogen olarak aşırı ekspresyon yoluyla meme karsinomu da dahil olmak üzere çeşitli kanserlerin patogenezine katkıda bulunmaktadır. Bu çalışmada, Türk popülasyonunda invaziv meme karsinomunda Cyclin D1 ekspresyonu ve klinikopatolojik önemi değerlendirildi. Yöntemler: 2007-2013 yılları arasında tanı konulan 143 hastaya ait parsiyel ve total mastektomi örneklerinden hazırlanan H&E ve immünohistokimyasal preparatlar incelendi. Cyclin D1 aşırı ekspresyonu, nükleer boyanma şiddetine (0-3) ve pozitif tümör hücrelerinin yüzdesine (1-3) dayalı IHC skoru kullanılarak 1000 hücrede değerlendirildi. Bulgular zayıf pozitif ('+' veya '++') veya güçlü pozitif ('+++') olarak sınıflandırıldı. Cyclin D1 ekspresyonu ile klinikopatolojik parametreler arasındaki ilişki, Pearson Ki-Kare ve Spearman rho testi kullanılarak analiz edildi. Bulgular: Hastaların medyan yaşı 58,5 yıl (Min: 28, Maks: 92) idi. Cyclin D1 durumu ile yaş, T evresi veya lenf nodu metastazı arasında anlamlı bir ilişki bulunmadı. Ancak, ER (r = 0,32, P < ,001) ve PR (r = 0,31, P <, 001) skorlarıyla orta derecede pozitif bir korelasyon gözlendi. Moleküler alt gruplar içinde, Cyclin D1 aşırı ekspresyonu en çok Luminal B grubunda (%92,9, P = ,008) saptandı ve Triple negatif grupta anlamlı derecede düşük ekspresyon (%40, P = ,008) gözlendi. Sonuç: Cyclin D1'in Luminal A ve Luminal B gruplarında aşırı ekspresyonu ve ER ile pozitif korelasyonu, bu proteinin östrojen duyarlı meme kanseri patogenezindeki rolünü düşündürmektedir. HER2-pozitif olgularda güçlü Cyclin D1 aşırı ekspresyonu, azalmış sağkalım süresi ile ilişkili bulunmuştur.

Keywords

• Meme
• invaziv meme karsinomu
• Cyclin D1
• histopatoloji
• immünohistokimya

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