Kolon adenokarsinomu ve prekanseröz lezyonlarında stıp1, beta-katenin ve siklin D1 ekspresyonunun değerlendirilmesi
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Dosyalar
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Kırıkkale Üniversitesi / Tıp Fakültesi / Tıbbi Patoloji Ana Bilim Dalı
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kolorektal karsinom (KRK), yılda 1,85 milyon yeni vaka ile dünyada ve Türkiye'de sık görülmektedir. KRK'ların büyük bir kısmı prekanseröz lezyonlar olan adenomlardan gelişmektedir. Adenom-karsinom gelişimindeki çok aşamalı sürecin en erken olayı APC gen mutasyonudur. Mutant APC, beta-kateninin sitoplazmada birikmesine ve nükleusa geçerek TCF/LEF trankripsiyon faktörleri üzerinden hücre proliferasyonunun artmasına neden olur. KRK'da prognoz; büyük ölçüde tümör evresini belirleyen barsak duvarına invazyon derinliği, lenf nodu metastazı, uzak metastaz varlığı ve histolojik dereceye bağlıdır. Ancak günümüzde tümörün tekrarlama veya ilerleme riskini öngörebilen güvenilir bir parametre bulunmamaktadır. Bu sebeple hastaların tedavi sonrası bireysel prognozunu tahmin edebilmek için gerçekleştirilecek araştırmalarla moleküler ve immünolojik belirteçlerin tanımlanması elzemdir. Bu çalışmada, kolon adenomatöz polipleri ve KRK'da; beta-katenin, siklin D1 ve Stres Kaynaklı Fosfoprotein 1 (STIP1) ekspresyonlarının belirlenmesi, söz konusu belirteçlerin adenom-karsinom sekansındaki potansiyel etkilerinin değerlendirilmesi ve KRK'da klinikopatolojik parametreler ile ilişkilerinin saptanması amaçlandı. Bu kapsamda STIP1 ekspresyonun beta-katenin ve siklin D1 ekspresyonları ile korelasyonu da değerlendirildi. Hastanemizde tanı almış 88 adet KRK, 20 adet tübüler adenom (TA), 20 adet villöz adenom (VA) ve 10 adet normal kolon mukozası olmak üzere toplamda 138 vaka patoloji raporları retrospektif taranarak çalışmaya dahil edildi. Olgulara immünohistokimyasal olarak beta-katenin, siklin D1 ve STIP1 boyaması uygulandı. Beta-katenin ve siklin D1 için nükleer, STIP1 için ise sitoplazmik boyanmalar değerlendirmeye alındı. Beta-katenin tümör dokusu ve adenomda, normal kolon mukozasına göre daha yüksek seviyede bulundu (p<0,001). TA grubunda KRK grubuna göre daha yüksek beta-katenin ekspresyonu görüldü (p=0,007). VA grubunda ise KRK grubuna göre anlamlı fark saptanmadı (p>0,05). Siklin D1 normal kolon mukozasına göre tümör dokusunda ve adenomda daha yüksek bulundu (sırasıyla p=0,013, p<0,001). TA ve VA grubunda, KRK grubuna göre siklin D1 daha yüksek düzeyde eksprese oldu (sırasıyla p=0,008, p=0,002). Lenfovasküler invazyon ve tümör depoziti olmayan tümörlerde yüksek düzeyde siklin D1 ekspresyonu saptandı (sırasıyla p=0,038, p=0,048). Ayrıca siklinD1 ekspresyonu ile lenf nodu metastazı arasında istatistiksel anlam düzeyine yakın (p=0,067, rho=- 0,196) negatif korelasyon gözlendi. Adenomda normal mukozaya göre daha yüksek bir STIP1 ekspresyon düzeyi saptanmış olmasına rağmen (p=0,007), tümör dokusu ile normal mukoza arasında anlamlı fark saptanmadı (p>0,05). STIP1 ekspresyonu; TA ve VA gruplarında, KRK grubuna göre yüksek bulundu (sırasıyla p<0,001, p=0,002). KRK grubunda beta-katenin, siklin D1 ve STIP1 ekspresyonu ile diğer klinikopatolojik özellikler arasında anlamlı ilişki saptanmadı (p>0,05). İmmünohistokimyasal markırların birbirleri ile ilişkileri değerlendirildiğinde; beta-katenin ile siklin D1 (p=0,025, rho=0,239), beta-katenin ile STIP1 (p=0,014, rho=0,261), siklin D1 ile STIP1 (p=0,001, rho=0,360) arasında anlamlı pozitif korelasyonlar saptandı. Siklin D1 ve beta-kateninin birlikte eksprese olduğu vakalarda daha düşük lenfovasküler invazyon (p=0,006), daha düşük pT evresi (p=0,085) görüldü. Elde edilen bulgular bir arada değerlendirildiğinde; KRK'da beta-katenin, siklin D1 ve STIP1 ekspresyonlarının birbiriyle ilişkili olduğu, STIP1'in Wnt/beta katenin sinyal yolağı üzerinden siklin D1 ekspresyonunu arttırarak adenomatöz dönüşümde rol oynayabileceği ve bu üç markırın tümörün invaziv aşamasında etkisini kaybettiği sonucuna varılmıştır. Sonuç olarak, KRK hastaları için prognostik belirteçler olarak siklin D1 ve beta-kateninin birlikte kullanılmasının prognozu tahmin etmede faydalı olabileceği değerlendirilmiştir. Anahtar kelimeler: Kolorektal karsinom, STIP1, siklin D1, beta-katenin, immünohistokimya.
Colorectal carcinoma (CRC) is common in the world and in Turkey with 1.85 million new cases per year. Majority of CRCs develop from adenomas which are precancerous lesions. The earliest event of the multistep process in adenoma carcinoma development is the APC gene mutation. Mutant APC causes beta-catenin to accumulate in the cytoplasm and translocate to the nucleus to increase cell proliferation through its interaction with the TCF/LEF transcription factors. The prognosis in CRC depends largely on the intestinal wall invasion depth, lymph node metastasis, presence of distant metastasis and histological grade which determine the tumor stage. However, today there is no reliable parameter that can predict the risk of recurrence or progression of the tumor. For this reason, it is essential to define molecular and immunological markers with studies to be performed in order to predict the individual prognosis of patients after treatment. In this study, it was aimed to determine the expressions of beta-catenin, cyclin D1 and Stress-Induced Phosphoprotein 1 (STIP1) in colon adenomatous polyps and CRC, to evaluate the potential effects of these markers on the adenoma-carcinoma sequence and to determine their relationship with clinicopathological parameters in CRC. In this context, the correlation of STIP1 expression with beta-catenin and cyclin D1 expressions was also evaluated. A total of 138 cases, including 88 CRCs, 20 tubular adenomas (TAs), 20 villous adenomas (VAs) and 10 normal colon mucosae diagnosed in our hospital, were retrospectively screened and included in the study. Immunohistochemically, beta catenin, cyclin D1 and STIP1 stainings were applied to the cases. Nuclear staining for beta-catenin and cyclin D1 and cytoplasmic staining for STIP1 were evaluated. Beta-catenin was found at higher levels in tumor tissue and adenoma than normal colon mucosa (p<0.001). Beta-catenin expression was higher in the TA group than in the CRC group (p=0.007). There was no significant difference in the VA group compared to the CRC group (p>0.05). Cyclin D1 was found higher in tumor tissue and adenoma than normal colon mucosa (p=0.013, p<0.001, respectively). Cyclin D1 was expressed at a higher level in the TA and VA group than in the CRC group (p=0.008, p=0.002, respectively). A high level of cyclin D1 expression was detected in tumors without lymphovascular invasion and tumor deposits (p=0.038, p=0.048, respectively). In addition, a negative correlation close to statistical significance (p=0.067, rho=-0.196) was observed between cyclin D1 expression and lymph node metastasis. Although a higher STIP1 expression level was detected in adenoma compared to normal mucosa (p=0.007), no significant difference was found between tumor tissue and normal mucosa (p>0.05). STIP1 expression was higher in TA and VA groups compared to the CRC group (p<0.001, p=0.002, respectively). In the CRC group, there was no significant relationship between beta-catenin, cyclin D1 and STIP1 expression and other clinicopathological features (p>0.05). When the relationships between immunohistochemical markers are evaluated, significant positive correlations between beta-catenin and cyclin D1 (p=0.025, rho=0.239), beta-catenin and STIP1 (p=0.014, rho=0.261), and cyclin D1 and STIP1 (p=0.001, rho=0.360) were detected. Less lymphovascular invasion (p= 0.006) and lower pT stage (p=0.085) were observed in cases where cyclin D1 and beta-catenin were co-expressed. When the obtained findings are evaluated together, it was concluded that beta catenin cyclin D1 and STIP1 expressions in CRC are interrelated, STIP1 may play a role in adenomatous transformation by increasing cyclin D1 expression through the Wnt/beta-catenin signaling pathway and these three markers lost their effect in the invasive phase of the tumor. In conclusion, it was evaluated that the concomitant use of cyclin D1 and beta-catenin which are prognostic markers for CRC patients may be beneficial for predicting prognosis. Keywords: Colorectal carcinoma, STIP1, cyclin D1, beta-catenin, immunohistochemistry.
Colorectal carcinoma (CRC) is common in the world and in Turkey with 1.85 million new cases per year. Majority of CRCs develop from adenomas which are precancerous lesions. The earliest event of the multistep process in adenoma carcinoma development is the APC gene mutation. Mutant APC causes beta-catenin to accumulate in the cytoplasm and translocate to the nucleus to increase cell proliferation through its interaction with the TCF/LEF transcription factors. The prognosis in CRC depends largely on the intestinal wall invasion depth, lymph node metastasis, presence of distant metastasis and histological grade which determine the tumor stage. However, today there is no reliable parameter that can predict the risk of recurrence or progression of the tumor. For this reason, it is essential to define molecular and immunological markers with studies to be performed in order to predict the individual prognosis of patients after treatment. In this study, it was aimed to determine the expressions of beta-catenin, cyclin D1 and Stress-Induced Phosphoprotein 1 (STIP1) in colon adenomatous polyps and CRC, to evaluate the potential effects of these markers on the adenoma-carcinoma sequence and to determine their relationship with clinicopathological parameters in CRC. In this context, the correlation of STIP1 expression with beta-catenin and cyclin D1 expressions was also evaluated. A total of 138 cases, including 88 CRCs, 20 tubular adenomas (TAs), 20 villous adenomas (VAs) and 10 normal colon mucosae diagnosed in our hospital, were retrospectively screened and included in the study. Immunohistochemically, beta catenin, cyclin D1 and STIP1 stainings were applied to the cases. Nuclear staining for beta-catenin and cyclin D1 and cytoplasmic staining for STIP1 were evaluated. Beta-catenin was found at higher levels in tumor tissue and adenoma than normal colon mucosa (p<0.001). Beta-catenin expression was higher in the TA group than in the CRC group (p=0.007). There was no significant difference in the VA group compared to the CRC group (p>0.05). Cyclin D1 was found higher in tumor tissue and adenoma than normal colon mucosa (p=0.013, p<0.001, respectively). Cyclin D1 was expressed at a higher level in the TA and VA group than in the CRC group (p=0.008, p=0.002, respectively). A high level of cyclin D1 expression was detected in tumors without lymphovascular invasion and tumor deposits (p=0.038, p=0.048, respectively). In addition, a negative correlation close to statistical significance (p=0.067, rho=-0.196) was observed between cyclin D1 expression and lymph node metastasis. Although a higher STIP1 expression level was detected in adenoma compared to normal mucosa (p=0.007), no significant difference was found between tumor tissue and normal mucosa (p>0.05). STIP1 expression was higher in TA and VA groups compared to the CRC group (p<0.001, p=0.002, respectively). In the CRC group, there was no significant relationship between beta-catenin, cyclin D1 and STIP1 expression and other clinicopathological features (p>0.05). When the relationships between immunohistochemical markers are evaluated, significant positive correlations between beta-catenin and cyclin D1 (p=0.025, rho=0.239), beta-catenin and STIP1 (p=0.014, rho=0.261), and cyclin D1 and STIP1 (p=0.001, rho=0.360) were detected. Less lymphovascular invasion (p= 0.006) and lower pT stage (p=0.085) were observed in cases where cyclin D1 and beta-catenin were co-expressed. When the obtained findings are evaluated together, it was concluded that beta catenin cyclin D1 and STIP1 expressions in CRC are interrelated, STIP1 may play a role in adenomatous transformation by increasing cyclin D1 expression through the Wnt/beta-catenin signaling pathway and these three markers lost their effect in the invasive phase of the tumor. In conclusion, it was evaluated that the concomitant use of cyclin D1 and beta-catenin which are prognostic markers for CRC patients may be beneficial for predicting prognosis. Keywords: Colorectal carcinoma, STIP1, cyclin D1, beta-catenin, immunohistochemistry.
Açıklama
Anahtar Kelimeler
Beta katenin = Beta catenin ; Kolon neoplazmları = Colonic neoplasms ; Prekanseröz durumlar = Precancerous conditions ; İmmünohistokimya = Immunohistochemistry Onaylandı Tıpta Uzmanlık Türkçe 2021 104 s.
