The relation of CD3, CD4, CD8 and PD-1 expression with tumor type and prognosis in epithelial ovarian cancers

Objectives: Ovarian cancer is a heterogeneous disease, where chronic inflammation plays a key role in carcinogenesis. In this study, it is aimed to analyze the relationship with prognosis and chemotherapy response to clinicopathologicalnvariables in epithelial ovarian cancers such as proliferation of PD-1 +, CD8 +, CD4 +, CD3 + T-lymphocytes infiltrating the tumor and tumor stroma.Material and methods: Seventy-six cases diagnosed with primary epithelial ovarian tumor from biopsy or surgical resection materials were included in the study. Immunreactivity of CD3, CD4, CD8, PD1 was evaluated immunohistochemically in lymphocytes in tumor infiltrating lymphocytes and stromal lymphocytes.Results: Seventeen (22.4%) of the cases were Type I, 59 (77.6%) of them were Type II ovarian carcinoma. PD-1 positivity was observed in stromal and intraepithelial lymphocytes in 22 (28.9%) of 76 cases. In the presence of PD-1 + T-lymphocytes that infiltrate tumor and stroma, disease-free survival are shorter (p = 0.037). The presence of stromal CD4 + and CD8 + T-lymphocytes was more common in late stage patients (p = 0.012, p = 0.036; respectively). The disease-free and overall survival rate was statistically significantly shorter in the presence of CD8 + T lymphocytes (p = 0.009, p = 0.003; respectively).Conclusions: CD3, CD4 and CD8 may contribute to PD-1 mediated tumor control. Anti PD-1 therapy may be an alternative to chemotherapy in PD-1 positive patients. Identifying patients who do not respond to chemotherapy through PD-1 expression prior to immunotherapy will help develop potential personalized immunotherapy

The relationship between immunohistochemical cd-3, cd-4, cd-5, cd-8 and pd-1 staining and histopathological diagnosis of cervical lesions in patients with abnormal colposcopic findings

Serviks kanseri halen dünyada en sık görülen kanserlerden biridir. Erken tarama yapılır ve etkili bir şekilde yönetilirse, en önlenebilir ve en başarılı şekilde tedavi edilebilen kanserdir. Serviks üzerinde bazı spesifik lezyonların kolposkopi sayesinde tanımlanması ve bu lezyonların servikal preinvazif ya da invazif hastalıklar ile olan ilişkisi nedeniyle kolposkopi daha da önemli hale gelmiştir. Son yıllarda, human papilloma virüs (HPV)’nin neden olduğu servikal kanser için immünoterapi çalışmalarında büyük ilerlemeler gerçekleşmiştir. Bu çalışma; anormal kolposkopik bulgusu olan hastaların, immünolojik alt yapısını ve immün boyamalar ile histopatolojik tanı ilişkisini ele almayı hedeflemektedir. Çalışma kapsamında 01 Ocak 2015 – 01 Kasım 2019 tarihleri arasında Pamukkale Üniversitesi Tıp Fakültesi Hastanesi Kadın Hastalıkları ve Doğum Kliniğine başvuran ve kolposkopi yapılmış hastalar retrospektif olarak incelenmiştir. Anormal kolposkopik bulguya sahip ve biyopsi alınmış olan hastalar çalışmaya alınmıştır. Tüm hastaların histopatolojik tanıları mevcut idi. 30 tane düşük dereceli skuamöz intraepitelyal lezyon (LGSIL) ve 30 tane yüksek dereceli skuamöz intraepitelyal lezyon (HGSIL) olmak üzere toplam 60 hasta çalışmaya dahil edildi. Pamukkale Üniversitesi Tıp Fakültesi Hastanesi Tıbbi Patoloji arşivindeki olgulara ait parafin bloklardan alınan yeni kesitlerde immünhistokimyasal CD3, CD4, CD5, CD8 ve PD1 ekspresyonları epitelde; tümörü infiltre eden lenfositlerde (TIL) ve stromada değerlendirilmiştir. Düşük dereceli skuamöz intraepitelyal lezyon (LGSIL) ve yüksek dereceli skuamöz intraepitelyal lezyon (HGSIL) tanısı konulmuş toplam 60 hastanın epitelyal ve stromal CD3, CD4, CD8, CD5 ve PD-1 immünhistokimya boyamaları yapılmıştır. Epiteldeki lezyon içerisinde tüm boyamaların ortalama boyanma endeksi HGSIL grubunda LGSIL grubundan fazla bulunmuştur; CD3 için 24,4 vs. 13,2 (p<0,001), CD4 için 10,57 vs. 5,37 (p=0,002), CD5 için 8,5 vs. 5,7 (p=0,006), CD8 için 13,87 vs. 7,67 (p<0,001), PD-1 için 1,83 vs. 0,27 (p=0,046). Stromada ise tüm diğer boyalar istatistiksel olarak HGSIL grubunda daha yüksek olmakla birlikte CD5 için benzer bulunmuştur. Genel olarak CD3, CD4 ve CD8 boyanma endeksi de Ki-67 ile pozitif korelasyon göstermektedir (Pearson korelasyon katsayıları CD3 için 0,51 (p<0,001); CD4 için 0,45 (p=0,002); CD8 için 0,49 (p<0,001)). CD3, CD4, CD5, CD8 ve PD-1 pozitif hücreler yüksek dereceli lezyonların epiteli içerisinde düşük dereceli lezyonlara kıyasla daha yüksek oranda bulunmaktadır. CD3, CD4 ve CD8 ise Ki-67 proliferasyon endeksi ile de pozitif korelasyon göstermektedir. Bu anlamda adı geçen markerların tanısal potansiyeli bulunmaktadır. Ancak bu ilişkinin prognoz açısından önemini değerlendirebilmek için daha geniş çalışmalara ihtiyaç vardır.Cervical cancer is still one of the most common cancers in the World. When cervical cancer is diagnosed early and managed effectively, which is one of the most preventable and successfully treated cancer types. Colposcopy has become even more important due to the identification of some specific lesions on the cervix by colposcopy and the relationship of these lesions with cervical preinvasive or invasive diseases. In recent years, great progress has been made in immunotherapy studies for cervical cancer caused by human papilloma virus (HPV). With this study, it aims to address the immunological background of patients with abnormal colposcopic findings and the relationship between immune staining and histopathological diagnosis. Patients who applied to Pamukkale University Medical Faculty Hospital Gynecology and Obstetrics Clinic between January 01, 2015 and November 01, 2019 were retrospectively analyzed. Patients with abnormal colposcopic findings and biopsy were included in the study. All patients had histopathological diagnoses. A total of 60 patients, 30 low-grade squamous intraepithelial lesions (LGSIL) and 30 high-grade squamous intraepithelial lesions (HGSIL) were included in the study. Immunohistochemical CD3, CD4, CD5, CD8 and PD1 expressions were evaluated in tumor infiltrate lymphocytes (TIL) and stroma in new sections taken from paraffin blocks of cases kept in the archive of Pamukkale University Medical Faculty Hospital Medical Pathology. A total of 60 patients diagnosed with low grade squamous intraepithelial lesion (LGSIL) and high grade squamous intraepithelial lesion (HGSIL) had epithelial and stromal CD3, CD4, CD8, CD5 and PD-1 immunohistochemistry staining. The average staining index of all staining within the lesion in the epithelium in the HGSIL group was higher than the LGSIL group; CD3; 24,4 vs. 13,2 (p<0,001), CD4; 10,57 vs. 5,37 (p=0,002), CD5; 8,5 vs. 5,7 (p=0,006), CD8; 13,87 vs. 7,67 (p<0,001), PD- 1; 1,83 vs. 0,27 (p=0,046). In stroma, all staining parameters were statistically higher in the HGSIL group, except CD5. In general, CD3, CD4 and CD8 staining index also correlated positively with Ki-67 (Pearson correlation coefficients 0.51 for CD3 (p <0.001); 0.45 (p = 0.002) for CD4; 0.49 for CD8 (p <0.001)). Higher amount of positive cells for CD3, CD4, CD5, CD8 and PD-1 are found in the epithelium of high-grade lesions compared to low-grade lesions. CD3, CD4 and CD8 also show a positive correlation with the Ki-67 proliferation index. In this sense, the mentioned markers may have diagnostic potential. However, larger studies are needed to evaluate the importance of this relationship in terms of prognosis