İlknur Türkmen

The Predictive and Prognostic Significance of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 Expression in Hepatocellular Carcinoma

Background Hepatocellular carcinoma (HCC) is the fifth most common fatal cancer and an important healthcare problem worldwide. There are many studies describing the prognostic and predictive effects of epidermal growth factor receptor 2 (c-erb-B2) and epidermal growth factor receptor 1 (EGFR), transmembrane tyrosine kinases that influence cell growth and proliferation in many tumors. Objectives The current study aimed to investigate the expression levels of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27, and ERCC1 in hepatocellular carcinoma (HCC) and their correlation with other clinicopathologic features. Patients and Methods Fifty HCC cases were stained immunohistochemically with these markers. Correlations between the markers and clinicopathologic characteristics and survival rates were analyzed. Results No membranous c-erb-B2 staining was seen, whereas cytoplasmic positivity was present in 92% of HCC samples, membranous EGFR was observed in 40%, PI3K was found in all samples, and mTOR was seen in 30%, whereas reduced or absent PTEN expression was observed in 56% of samples and loss of p27 was seen in 92% of the cases. c-erb-B2 and mTOR overexpression, as well as reduced expression of p27, all correlated with multiple tumors (P = 0.041, P < 0.001, and P < 0.001, respectively). P27 loss, and mTOR and EGFR positivity were significantly correlated with AFP (P = 0.047, P = 0.004, and P = 0.008, respectively). Angiolymphatic invasion was more commonly seen in EGFR- and ERCC1-positive cases (P = 0.003 and P = 0.005). EGFR was also correlated with histological grade (P = 0.039). No significant correlations were found among PTEN , PI3K, and the clinicopathological parameters. Disease-free or overall survival rates showed significant differences among therapy modalities, AFP levels, angiolymphatic or lymph node invasions, and ERCC1 and p27 expression levels (P < 0.05). Conclusions c-erb-B2, EGFR, mTOR, ERCC1 overexpression levels, and loss of p27 may play roles in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior. These markers were found to be correlated with certain clinicopathologic features, therapy modalities, and survival rates in the current study. These findings may help in planning new, targeted treatment strategies .

Comparison of KRAS Mutation Tests in Colorectal Cancer Patients

The KRAS pathway and studies evaluating KRAS as a prognostic marker in colorectal cancer are discussed along with advances in KRAS gene mutation testing. Highly sensitive real-time polymerase chain reaction (PCR) methods were developed for this purpose. We examined the applicability of direct sequencing and two real-time PCR methods in the diagnosis of KRAS mutations. We used real-time PCR and direct sequencing-based methods to determine applicability of these KRAS mutation tests in 64 colorectal cancers. The two DNA samples found to be mutation positive by real-time PCR were analyzed again after diluting 100-fold. The results were the same. When we applied the same strategy for the direct sequencing, even a 10-fold dilution did not show the mutations. Therefore, we found that sequencing may not be informative when there are only a few mutant cells in the tumor. KRAS mutation screening on formalin-fixed, paraffin-embedded DNA is very efficient with real-time PCR methods in comparison to direct sequencing. The development and adoption of guidelines for KRAS mutation testing are crucial for success.

Xanthomatous hyperplastic polyps of the stomach: clinicopathologic study of 5 patients with polypoid gastric lesions showing combined features of gastric xanthelasma and hyperplastic polyp

Gastric xanthelasmas are uncommon benign lesions that are macroscopically well-demarcated yellow or yellow-white plaques and are microscopically formed by collections of foamy macrophages. Because gastric hyperplastic polyps may rarely be associated with xanthelasma, we aimed to report 5 cases of combined lesions showing features of gastric xanthelasma and hyperplastic polyps observed over the past 3 years at our institution among 4497 patients who underwent gastric endoscopy. The patients were 3 men and 2 women aged 45 to 78 years. The lesions were located in oxyntic mucosa, except one in the antrum, and measured 2 to 6 mm. Three patients showed associated chronic gastritis; none showed evidence of Helicobacter pylori infection. Combined lesions of hyperplastic polyp with xanthelasma appear to have an association with chronic gastritis, and the lipid accumulation may be the cause of hyperplasia in the overlying mucosa.

Patients with epithelial cell abnormality in PAP smears: correlation of results with follow-up smears and cervical biopsies.

Abstract Objective: Cervical carcinoma has been included in the preventable diseases category ever since the use of cervical cytology in routine practice. The Pap test is an efficient screening test. We aimed to compare the cervical cytology diagnosis with biopsy and smear follow up results in our institution. Material and Method: We aimed to compare the diagnosis of cytology material examined in our institution during the 2009-2012 period with their biopsy and smear follow ups. The diagnoses were compared with the follow up smears and/or cervical biopsies. Results: 13610 Pap tests were examined during September 2009-July 2012. Among these cases, there were 370 atypical squamous cells of undetermined significance (ASCUS), 29 atypical squamous cells-high grade intraepithelial lesions cannot be excluded (ASC-H), 155 low grade squamous intraepithelial lesion (LSIL), 33 high grade squamous intraepithelial lesion (HSIL), and 5 atypical glandular cell (AGC) diagnoses. The ratio of atypical squamous cell (ASCUS and ASC-H) to squamous intraepithelial lesions was 2.12. Squamous intraepithelial lesion was verified in 47 of 91 ASCUS cases. Among patients who had a cervical biopsy, 52 of 64 LSIL cases and all of the 21 HSIL cases had biopsy-proven SIL. Conclusion: Atypical squamous cell (ASC) is the most common diagnosis in abnormal cervical cytology. As it is indefinite, ASC is used as a quality assurance parameter and the aim is to decrease its use. As the ratio of epithelial cell abnormality is variable in different populations, the ASC/SIL is a more definite variable to be used for quality assurance. The efficiency in clinical use of the cervical cytology screening test is determined by biopsy verification. Our epithelial cell abnormality, ASC/SIL ratio and cytology-histology correlation values were parallel to the literature, proving that the methods are used reliably at our institution. Öz Amaç: Servikal sitolojinin rutin pratikte kullanılması ile birlikte serviks karsinomu önlenebilir hastalıklar içine girmiştir. Pap smear etkin bir tarama testidir. Bölümümüzde incelenen servikal sitoloji materyallerinin tanıları ile biyopsi ve smear takip sonuçları karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Bu çalışmada 2009-2012 yılları arasında bölümümüzde yapılan servikal sitoloji sonuçları gözden geçirilmiştir. Tanılar, kontrol smear tekrarı ve/veya biyopsi sonuçları ile karşılaştırılmıştır. Bulgular: Bölümümüzde Ekim 2009-Temmuz 2012 tarihleri arasında 13.610 adet Pap smear raporu incelenmiştir. Bu olgular içinde 370 önemi belirlenemeyen atipik skuamöz hücre (ASCUS), 29 yüksek dereceli skuamöz intraepitelyal lezyonun ekarte edilemediği atipik skuamöz hücre (ASC-H), 155 düşük dereceli skuamöz intraepitelyal lezyon (LSIL), 33 yüksek dereceli skuamöz intraepitelyal lezyon (HSIL), 5 atipik glandüler hücre (AGH) saptanmıştır. Atipik skuamöz hücrenin (ASCUS ve ASC-H tanılarının toplamı) skuamöz intraepitelyal lezyona oranı (ASC/SIL) 2,12’ dir. Biyopsi yapılan 91 adet ASCUS olgusunun 47’sinde SIL saptanmıştır. Biyopsi yapılan 64 adet olgusunun 52’sinde LSIL; 21 adet olgusunun tamamında HSIL tanısı doğrulanmıştır. Sonuç: Atipik skuamöz hücre (ASH) anormal servikal sitolojideki en sık tanıdır. Belirsizlik ifade ettiği için fazla kullanımı önlenmeye çalışılmaktadır ve kalite kontrolünde kullanılmaktadır. Farklı toplumlarda, Epitel Hücre Anomalisi (EHA) oranı değişken olabildiği için, ASH/SIL oranı kalite yönetimi açısından daha net bir veri olarak değerlendirilmektedir. Bir tarama testi olan servikal sitolojinin klinik uygulamalarda güvenilir şekilde kullanımı ise biyopsi doğrulaması ile mümkündür. Serimizde EHA yüzdesi, ASC/SIL oranı ve smear ile biyopsi arasındaki uyum sonuçları literatür ilgilerine paralel olup, merkezimizde güvenilir bir yöntem olarak kullanılmaktadır

General evaluation of hepatectomy and hepatocellular carcinoma cases.

OBJECTIVE Although the clinical and histopathological findings of hepatocellular carcinoma are well described, there are few national studies. In this study, we aimed to investigate the relationship between these findings in total or partial hepatectomy specimens in our series. MATERIAL AND METHOD We first collected 190 cases of total or partial hepatectomies performed because of hepatocellular carcinoma, cirrhosis or other disorders from the archives of Pathology. After re-examining the histopathological and clinical features such as age, gender and etiology, the relationship between them and serology results were statistically analyzed using the chi square and Multiple Comparison Tests. RESULTS Among 190 cases, there were 168 (88.5%) total and 18 (9.5%) partial hepatectomies and 4 (2%) tumorectomy or metastasectomy cases. After gross and microscopic examination, 170 (89.5%) cases had a diagnosis of cirrhosis, 85 (44.7%) hepatocellular carcinoma, 3 parasitic cyst, 7 metastasis, 1 hepatoblastoma, 1 hepatocellular adenoma, 2 cholangiocarcinoma, 2 Budd Chiari Syndrome, 1 focal nodular hyperplasia, 1 cavernous hemangioma, and 2 acute fulminant hepatitis. Among the hepatocellular carcinoma cases, 53 had Hepatitis B virus, 15 Hepatitis C virus , 3 Hepatitis B virus and Hepatitis C virus, and 3 Hepatitis B virus and Hepatitis delta virus etiology, while 6 were alcoholic and 4 were due to other causes. Among cirrhosis patients, 84 (49.4%) had hepatocellular carcinoma. The male to female ratio of hepatocellular carcinoma cases was 74/11. The mean age was 55 and the median age 56.7. CONCLUSION The results of this study demonstrated that the most common hepatic disorder was cirrhosis due to Hepatitis B virus in the hepatectomy specimens of our series that mostly consisted of total hepatectomies performed for transplantation where 50% had hepatocellular carcinoma.

Endocervical glandular involvement, multicentricity, and extent of the disease are features of high-grade cervical intraepithelial neoplasia.

This study aimed to evaluate the rate of endocervical glandular involvement, positive surgical margins, multicentricity, and disease extent between low-grade and high-grade cervical intraepithelial lesions after loop electrosurgical excision procedure (LEEP). Pathology medical records of patients who underwent LEEP were reviewed retrospectively. Patients with negative LEEP results were excluded. Loop electrosurgical excision procedure reports of patients with cervical intraepithelial neoplasia (CIN) 1, 2, and 3 were compared. There was no statistically significant difference between patients with CIN 1 (n=24), CIN 2 (n=27), and CIN 3 (n=64) when age and surgical margin positivity were considered. Endocervical glandular involvement, multicentricity, and disease extent were higher in patients with CIN 3 (P=.001, P=.002, and P=.001, respectively). In conclusion, we recommend that patients with endocervical glandular involvement, lesions involving more than two-thirds of the LEEP specimen, and multicentricity be followed up more closely.

A deep learning based approach for classification of CerbB2 tumor cells in breast cancer

This study proposes a unique approach to classify CerbB2 tumor cell scores in breast cancer based on deep learning models. Another contribution of the study is the creation of a dataset from original breast cancer tissues. On the purpose of training, validating and testing with deep learning models cell fragments were generated from sample tissue images. CerbB2 tumor scores were generated for the cell fragments were classified with high performance by the aid of convolutional neural networks (CNN).

Segmentation of precursor lesions in cervical cancer using convolutional neural networks

Cervical carcinoma is one of the frequently seen cancers in the world and in our country, develops from precursor lesions. These precursor lesions are analyzed by pathologists so that the diagnosis of the disease can be made. In this study, a system that performs automatic detection of pre-cancerous lesions was performed using the convolutional neural networks (CNNs). In the training phase, lesion recognition performance of the proposed system has reached 92%. Thereafter, whole image was segmented by using 60 × 60 pixel tiles during the training phase. After all, the precursor lesions were segmented with 81.71% Dice coefficient.

A multi-level thresholding based segmentation method for microscopic fluorescence in situ hybridization (FISH) images

Fluorescence in situ hybridization (FISH) technique widely used in cancer diagnosis is based on displaying chromosomal regions as FISH signals by staining with specific dyes. In this study, a new multi-level thresholding based FISH signal segmentation method is proposed for images produced by FISH technique. Cell nuclei are segmented on images, that are grabbed from fluorescence microcopes at high resolution, with adaptive thresholding, distance transform and watershed methods. FISH signals falling in cell boundaries are detected by applying multi-level thresholding and morphological post processes thanks to proposed segmentation method. It is observed that the detection rate of the proposed method on 49 FISH images taken from real patients, are higher than other widely used techniques in the literature.

What does the data of 354,725 patients from turkey tell US about cervical smear epithelial cell abnormalities? - the epithelial cell abnormality rate is increasing - quality control studies and corrective activity are musts

OBJECTIVE There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.