Endometrial Karsinomlarda İmmünhistokimyasal Lipin-1 Ekpresyonunun Değerlendirilmesi ve Prognostik Verilerle İlişkisi
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Tarih
2024
Yazarlar
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Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Endometrial kanser (EMK), kadınlarda görülen jinekolojik kanserler arasında en yaygın
olanlarından biridir. Uluslararası Kanser Araştırma Ajansı (IARC) bünyesindeki Global
Kanser Gözlemevi (GCO) tarafından yayımlanan GLOBOCAN 2020 istatistiklerine göre,
endometrial kanser dünya genelinde 417.000 yeni tanı ve 97.000 ölümle, kadınlarda altıncı
en sık rastlanan kanser türüdür ve kadın kanserlerinin yaklaşık %4,5'ini temsil etmektedir.
Diğer birçok kanser türünün aksine, son yirmi yıl içinde insidans oranlarında düşüş
gözlemlenirken, endometrial kanserin insidansı yükselmeye devam etmektedir. Kanser
hücreleri, normal hücrelere kıyasla, genellikle metabolik yolları değiştirerek çalışır. Bu, yeni
moleküler yapıların üretilmesi ve artan enerji taleplerinin karşılanması amacıyla yapılır. Bu
süreç, özellikle metastaz yapabilme ve hızlı büyüme yetenekleri için gerekli olan
organellerin üretimini sağlayacak yeni membranların üretilmesi için lipid metabolizmasının
yeniden düzenlenmesini içerir. Bu süreç için, yağ asitlerinin ve kolesterolün alımı veya
sentezi gerekir. Lipin ailesi olarak bilinen ve üç üyesi bulunan (lipin-1, lipin-2, lipin-3)
fosfatidik asit fosfataz (FAF), bu mekanizmada kritik bir role sahiptir. Lipin-1'in enzimatik
aktivitesi, hücre farklılaşmasını, inflamasyonu ve otofajiyi içeren çeşitli yolları hızlandırarak
karsinogenezis (kanser oluşumu) sürecini tetikler. Bu nedenle, lipinler ve lipid biyosentezini
düzenleyen diğer enzimler, geliştirilmekte olan kanser terapilerinde hedeflenmesi muhtemel
önemli faktörler arasındadır.Lipin-1 ile alakalı daha önce akciğer, prostat ve meme
karsinomlarında çalışmalar mevcut olup lipin-1 inhibitörleri bu tümörlerin tedavisinde
kullanılmaya başlanmıştır. Çalışmamızda Necmettin Erbakan Üniversitesi Tıp Fakültesi
Tıbbi Patoloji Anabilim Dalı’nda EMK tanısı almış olgular değerlendirildi. Olgulara
immünhistokimyasal olarak Lipin-1 boyası uygulandı. Elde edilen veriler klinikopatolojik
parametrelerle istatistiksel olarak karşılaşıltırıldı. Lipin-1 ile tümör derecesi arasında orta
düzeyde ve istatistiksel olarak anlamlı bir pozitif korelasyon saptanmıştır (r = 0.284, p =
0.004). Lipin-1 ile hasta yaşları arasında anlamlı bir fark bulunmuştur (p = 0.020). Yoğun
boyanan grup en yüksek ortalama yaşa sahiptir. Lipin-1 ile FIGO evresi evresi açısından
gruplar arasında anlamlı farklar bulunmuştur (p = 0.032). Yoğun boyanan grupta daha ileri
evreler sık görülmüştür. FIGO evresi ile tümör derecesi arasında güçlü ve istatistiksel olarak
çok anlamlı bir pozitif korelasyon gözlenmiştir (r = 0.693, p < 0.001). FIGO evresi ile lenf
nodu metastazı arasında da güçlü ve istatistiksel olarak anlamlı bir pozitif korelasyon
bulunmuştur (r = 0.720, p < 0.001). Tümör derecesi ile lenf nodu metastazı arasında orta
düzeyde ve istatistiksel olarak anlamlı bir pozitif korelasyon tespit edilmiştir (r = 0.315, p =
0.001). Tümör derecesi ile yaş arasında da orta düzeyde ve istatistiksel olarak anlamlı bir
pozitif korelasyon saptanmıştır (r = 0.380, p < 0.001). Lenf nodu metastazı ile tümörün en
uzun çapı arasında düşük düzeyde fakat istatistiksel olarak anlamlı bir pozitif korelasyon
mevcuttur (r = 0.209, p = 0.037). Lipin-1 ile endometrioid ve seröz tip kanserler açısından
gruplar arasında anlamlı bir farklılık yoktur (p = 0.305). Daha önce literatürde EMK ile ilgili
çalışma bulamadığımız Lipin-1 molekülü ile EMK anlamlı sonuçlar elde edilmiş olup bu
molekülün tedavi aşamasında kullanılabileceğini düşünmekteyiz.
Endometrial cancer is one of the most common gynecological cancers in women. According to GLOBOCAN 2020 statistics published by the Global Cancer Observatory (GCO) within the International Agency for Research on Cancer (IARC), endometrial cancer is the sixth most common cancer type in women, with 417,000 new diagnoses and 97,000 deaths worldwide, representing approximately 4.5% of women's cancers. Unlike many other types of cancer, while incidence rates have decreased over the past two decades, the incidence of endometrial cancer continues to rise. Cancer cells, compared to normal cells, often work by altering metabolic pathways. This is done in order to produce new molecular structures and meet increasing energy demands. This process involves the reorganization of lipid metabolism to produce new membranes that will enable the production of organelles, especially those required for metastasis and rapid growth abilities. This process requires the uptake or synthesis of fatty acids and cholesterol. Phosphatidic acid phosphatase (FAF), known as the lipin family and having three members (lipin-1, lipin-2, lipin-3), has a critical role in this mechanism. The enzymatic activity of Lipin-1 triggers the process of carcinogenesis by accelerating various pathways including cell differentiation, inflammation and autophagy. Therefore, lipins and other enzymes that regulate lipid biosynthesis are among the important factors that are likely to be targeted in cancer therapies being developed. There are previous studies on Lipin-1 in lung, prostate and breast carcinomas, and lipin-1 inhibitors have begun to be used in the treatment of these tumors. In our study, cases diagnosed with endometrial carcinoma at Necmettin Erbakan University Faculty of Medicine, Department of Medical Pathology were evaluated. Lipin-1 staining was applied to the cases immunohistochemically. The obtained data were compared statistically with clinicopathological parameters. A moderate and statistically significant positive correlation was detected between Lipin-1 and tumor grade (r = 0.284, p = 0.004). A significant difference was found between Lipin-1 and patient ages (p = 0.020). The intensely staining group has the highest mean age. Significant differences were found between groups in terms of lipin-1 and FIGO stage (p = 0.032). More advanced stages were common in the intensely staining group. A strong and statistically significant positive correlation was observed between FIGO stage and tumor grade (r = 0.693, p < 0.001). A strong and statistically significant positive correlation was also found between FIGO stage and lymph node metastasis (r = 0.720, p < 0.001). A moderate and statistically significant positive correlation was detected between tumor grade and lymph node metastasis (r = 0.315, p = 0.001). A moderate and statistically significant positive correlation was also detected between tumor grade and age (r = 0.380, p < 0.001). There is a low but statistically significant positive correlation between lymph node metastasis and the longest diameter of the tumor (r = 0.209, p = 0.037). There is no significant difference between groups in terms of Lipin-1 and endometrioid and serous type cancers (p = 0.305). Significant results were obtained with the Lipin-1 molecule, which we could not find any studies on endometrial carcinoma in the literature before, and we think that this molecule can be used in the treatment phase.
Endometrial cancer is one of the most common gynecological cancers in women. According to GLOBOCAN 2020 statistics published by the Global Cancer Observatory (GCO) within the International Agency for Research on Cancer (IARC), endometrial cancer is the sixth most common cancer type in women, with 417,000 new diagnoses and 97,000 deaths worldwide, representing approximately 4.5% of women's cancers. Unlike many other types of cancer, while incidence rates have decreased over the past two decades, the incidence of endometrial cancer continues to rise. Cancer cells, compared to normal cells, often work by altering metabolic pathways. This is done in order to produce new molecular structures and meet increasing energy demands. This process involves the reorganization of lipid metabolism to produce new membranes that will enable the production of organelles, especially those required for metastasis and rapid growth abilities. This process requires the uptake or synthesis of fatty acids and cholesterol. Phosphatidic acid phosphatase (FAF), known as the lipin family and having three members (lipin-1, lipin-2, lipin-3), has a critical role in this mechanism. The enzymatic activity of Lipin-1 triggers the process of carcinogenesis by accelerating various pathways including cell differentiation, inflammation and autophagy. Therefore, lipins and other enzymes that regulate lipid biosynthesis are among the important factors that are likely to be targeted in cancer therapies being developed. There are previous studies on Lipin-1 in lung, prostate and breast carcinomas, and lipin-1 inhibitors have begun to be used in the treatment of these tumors. In our study, cases diagnosed with endometrial carcinoma at Necmettin Erbakan University Faculty of Medicine, Department of Medical Pathology were evaluated. Lipin-1 staining was applied to the cases immunohistochemically. The obtained data were compared statistically with clinicopathological parameters. A moderate and statistically significant positive correlation was detected between Lipin-1 and tumor grade (r = 0.284, p = 0.004). A significant difference was found between Lipin-1 and patient ages (p = 0.020). The intensely staining group has the highest mean age. Significant differences were found between groups in terms of lipin-1 and FIGO stage (p = 0.032). More advanced stages were common in the intensely staining group. A strong and statistically significant positive correlation was observed between FIGO stage and tumor grade (r = 0.693, p < 0.001). A strong and statistically significant positive correlation was also found between FIGO stage and lymph node metastasis (r = 0.720, p < 0.001). A moderate and statistically significant positive correlation was detected between tumor grade and lymph node metastasis (r = 0.315, p = 0.001). A moderate and statistically significant positive correlation was also detected between tumor grade and age (r = 0.380, p < 0.001). There is a low but statistically significant positive correlation between lymph node metastasis and the longest diameter of the tumor (r = 0.209, p = 0.037). There is no significant difference between groups in terms of Lipin-1 and endometrioid and serous type cancers (p = 0.305). Significant results were obtained with the Lipin-1 molecule, which we could not find any studies on endometrial carcinoma in the literature before, and we think that this molecule can be used in the treatment phase.
Açıklama
Anahtar Kelimeler
Endometrial kanser, Endometrial cancer, Lipin-1, immünhistokimya, immünhistochemicestry, kanser, cancer
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Yılmaz, O. (2024). Endometrial Karsinomlarda İmmünhistokimyasal Lipin-1 Ekpresyonunun Değerlendirilmesi ve Prognostik Verilerle İlişkisi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Tıp Fakültesi Cerrahi Tıp Bilimleri Bölümü Tıbbi Patoloji Anabilim Dalı, Konya.
