The cancer stem cells (CSCs) represent a minority of tumor cells that are able to proliferate and self-renew and might be responsible for tumor initiation and maintenance. The CD133 and CD117 are the ...most commonly used markers for the putative CSCs, especially for the ovarian CSCs, but its clinical significance remains uncertain. The aim of this study was to compare the immunohistochemical expression of CD133 and CD117 in 64 primary ovarian high grade serous carcinoma and peritoneal metastasis, and to examine their potential clinical role. CD133 expression was mainly seen in the apical/endoluminal cell surface of tumor cells and was found in 61% of the carcinoma samples and 41% of the metastasis. The median of CD133 positive cells in tumors was 1 (0.1-7)%, and in metastases was 0.6 (0.1-6)%. CD117 expression appeared as a cytoplasmic and/or membranous stain and was found in 81% of the carcinoma samples and 77% of the metastasis. The median of CD117 positive cells in tumors was 1 (0.1-8)%, and in metastases was 0.1 (0.1-7)%. Multivariate analysis has shown that patients with high CD133 expression in tumor cells have significantly shorter disease free survival and overall survival (p=0.025 and p=0.014, respectively). Patients with high CD117 expression in tumor cells have significantly shorter disease free survival (p=0.031). Cox's proportional hazards model identified expression of CD133 protein in tumor as an independent prognostic factor. Our study indicates that the immunohistochemical assessment of CD133 and CD117 expression may have potential clinical value in predicting disease progression and prognosis in the high grade serous ovarian cancer. CD133 proved to be an independent prognostic factor in the high grade serous ovarian cancer patients.
The majority of endometrial carcinoma are diagnosed at an early stage and exhibit a favorable prognosis. However, 10% to 15% of ECs recur and the majority are type II tumors which are high-grade ...carcinomas. The epithelial-mesenchymal transition (EMT) has been considered as a fundamental step for the development of the invasive phenotype of cancer cells. During EMT, many of epithelial surface markers, primarily E-cadherin disappear, and mesenchymal markers including N-cadherin gain. This feature resides predominantly at the invasive front (IF) of the tumor. Therefore, we examined the immunohistochemical expression of E-cadherin and N-cadherin at the IF, in central areas of the tumor and lymphovascular space, in type I and type II endometrial carcinoma. The association of each protein with the clinicopathologic features was also evaluated. Our results confirmed a stronger E-cadherin immunostaining in type I tumors indicating that the loss of E-cadherin may be responsible for a more aggressive behavior of type II ECs. In both types, E-cadherin was strongly expressed in central areas and the reactivity decreased toward the IF. On contrary, N-cadherin was overexpressed at the IF confirming an inverse relationship between these markers. In addition, a decrease in E-cadherin expression was observed in cells within the lymphovascular space. Downregulation of E-cadherin was associated only with high-grade tumors while no correlations between both markers and other clinicopathologic features were found. Our results confirm that EMT occurs at the IF that represents a critical interface between the tumor and the host.
Objective: The aim of the study was to evaluate the accuracy of the diagnostic Pap test (DPT) on three slides and punch biopsy and endocervical curettage (PB/ECC) compared with the final biopsy ...material in the detection of high-grade squamous intraepithelial lesion (HSIL). Materials and methods: Patients treated with conization after previous DPT and PB/ECC were analyzed. The findings of the DPT and PB/ECC as well as of the endocervical brush cytology and ECC were compared with the final conus histology. Results: 150 patients were analyzed, and final histology verified 145 cases of HSIL and 3 cancers. The percentage of confirmed HSIL cytology was 97%, while for PB/ECC it was 79% with 30/145 false negative results. The correlation between Pap test and PB/ECC showed that the diagnostic accuracy of DPT is significantly higher (p < 0.0001). Endocervical brush cytology confirmed HSIL+ in the endocervical canal in 83% and ECC in 35% of cases (p < 0.0001). Conclusion: The DPT on three slides enables better detection of HSIL compared to PB/ECC, particularly for lesions localized in the endocervical canal sampled with a cytobrush. A high quality DPT could represent a surrogate for PB/ECC and open the possibility of direct access to therapeutic procedure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears years before invasive squamous cancer arises, but no reproducible morphologic criteria exist to predict behavior of ...cervical lesions. The possibility of predicting the clinical course of cervical lesions could be of high value in clinical practice and some women will spare of unnecessary treatment. HPV L1 capsid protein represents about 90% of the total protein on the surface of the virus and can be detected in mild to moderate dysplasia and rarely in severe dysplasia. The purpose of the study was to evaluate the use of immunodetection of HPV L1 protein on archival Pap smears with findings of mild and moderate dysplasia in predicting its clinical course. Immunochemical analyses with L1 antibody revealed positively stained nuclei of squamous epithelial cells in 56 of 114 smears (49.1%). The staining results were correlated with follow-up smears or with histologic verification. Regression (negativisation of the Pap smear for 24 months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of 58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1-positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The difference in the clinical course between the L1-positive and L1-negative patients was statistically significant (p = 0.025). Also, the difference in the clinical course of the L1-negative staining in the under-30 and over-30 years age group was statistically significant (p = 0.04). For conclusion, our data confirm that immunostaining for HPV L1 capsid protein could offer prognostic information about mild and moderate intraepithelial cervical squamous lesions.
The patients treated with conservative surgical therapy for cervical intraepithelial neoplasia (CIN) have an increased risk to develop invasive cervical carcinoma compared to the general population. ...Cervical cytology and HPV test are included in the protocols for the detection of treatment failure. The purpose of the study was to analyse cytology-histology correlation after conisation or Large Loop Excision of the Transformation Zone (LLETZ), resection margin status, compliance to the follow-up protocol and evaluation of cervical cytology and HPV testing in two year period after surgical treatment. We retrospectively reviewed 251 cases of conisation or LLETZ performed between January and December, 2006. Conventional cervical smears were analysed and abnormal cytology was defined as atypical squamous cells of undetermined significance or worse (ASCUS+). The digene Hybrid capture 2 test was used for detection of high-risk HPV types. Histology analysis demonstrated CIN1 + lesion in 234 cases (93.2%) with cytology-histology correlation in 97.9% of cases. A preoperative HPV test was made in 142 histologically confirmed CIN1 + lesions and 137 (96.5%) tested positive. The resection margins were involved in 48 (20.8%) cases. In 24 (10.3%) cases the margins were difficult to determine. Abnormal cytology was found in 33 (15.2%) cases of the 217 (86.5%) patients that attended the post-treatment visits. The post-treatment HPV test was performed on 159 women and it was positive in 25 (15.7%) cases. The complete follow-up control cytology, with at least three Pap smears in the subsequent two years or with second treatment, was registered in only 146 (58.2%) patients. 14/217 (6.5%) patients underwent second treatment with histologically confirmed treatment failure. In all patients with control smear, repeated cytology found HSIL. On six women, the control HPV test was performed. In five cases, it was positive and in one case with histological diagnoses of VAIN2, it was negative. Our study confirms the important role of cervical cytology in the diagnosis of cervical intraepithelial lesions and monitoring after treatment. In the future we will have to improve compliance to the follow-up protocols and use of the HPV test in the selection of women at risk of treatment failure.
The opportunistic cervical cancer screening has been conducted in Croatia since its introduction in the 1960s, in the context of a high quality gynaecological cytology with a long tradition and a ...wide network of primary care gynaecologists. In 2006, a pilot screening programme under the title "Early detection of cervical cancer was conducted in Primorsko-Goranska County (PGC)", as the first organised cervical cancer screening ever conducted in the Republic of Croatia. The pilot screening programme targeted women aged 20-64 years. The pilot group consisted of 6,000 randomly sampled primary care patients of six gynaecologists. The women were invited via a personal letter and were given a questionnaire. The results of the first and the second year of screening, as well as of both years together were analysed. The response rate to the anamnestic questionnaire was 49.1%. The participation rates to the screening were 35.2% in 2007, and 46.5% in 2008, total of 42.7%. The increase in participation between years 2007 and 2008 was statistically significant (p = 0.01). According to the age, the lowest participation rate of 33.3% was observed in the youngest group of women (20-29) and the highest of 60.7% in the oldest group (60-64). The detection rate of cytological abnormalities was 4.6% with 2.6% of borderline (ASCUS) cytology and referral rate of 1.2%. The highest abnormal Pap test frequencies of 6.8% and 7.1% were observed in the youngest age groups (20-29 and 30-39), and the lowest (2%) in the age group of 60-64. Specimen adequacy was generally of high quality with unsatisfactory rate of 0.8%, with statistically significant improvement in 2008, compared to the previous year (p = 0.001). Although to a limited extension, during two-year pilot cervical cancer screening programme in PGC the participation rates and Pap smear adequacy have improved. We expect that the continuation of the programme will result in further increase of participation and higher overall quality of the programme.
Villoglandular papillary adenocarcinoma (VGA) of cervix is an uncommon but well recognized histologic subtype of cervical adenocarcinoma which usually affects young women. Based on the favorable ...outcomes reported in most previous cases the tumor is generally considered to have an indolent clinical course with excellent prognosis. We present a case of a 22-year-old woman admitted at our Department for glandular abnormality on cervical smear and episodes of vaginal discharge. In the Pap smear, the cytological features were suspicious but not diagnostic of adenocarcinoma, therefore reported as atypical glandular cells (AGC). Histological examination confirmed VGA associated with lymphovascular space invasion. The patient underwent radical operative procedure. Intraoperative cytologic examination detected pelvic lymph nodes metastasis. The patient was confirmed to be in an advanced stage - III B (FIGO). During a two years follow-up period a rapid dissemination of the tumor occurred and resulted with a fatal outcome. Although VGA has been reported to have a favorable prognosis, several cases with lymph node involvement have already been described. Cervical smears examination would be helpful for an early diagnosis of VGA, however the cytologic recognition is often difficult. Further investigation of the pathogenesis, diagnosis and therapy of the tumor is needed.
To determine the morphometric characteristics of nuclei and silver-stained nucleolar organizer regions (AgNORs) on cytologic imprints and their value in differential cytodiagnosis of benign, atypical ...proliferative (borderline) and malignant ovarian mucinous tumors.
Forty-six mucinous ovarian tumor imprints (16 benign, 15 borderline, 15 malignant), were analyzed. Nuclear area, outline, "shape factor" and "form factor" were measured on Papanicolaou-stained smears. AgNOR quantification included 7 variables related to the number and area of single, cluster, total and relative AgNOR content per nucleus and the size distribution of AgNORs.
Nuclear area and shape factor allowed distinguishing borderline and malignant tumors. The nuclear area in benign tumors was larger than that in borderline tumors; malignant tumors had the highest values. Single and cluster AgNORs were statistically significantly different in borderline tumors compared with malignant tumors, except for the cluster AgNOR area. The total AgNOR area, number and relative area increased from benign through malignant tumors, with statistically significant differences among all groups. By AgNOR size distribution, small AgNORs discriminate malignant from borderline and benign tumors.
Combining nuclear morphometry and AgNOR analysis on cytologic imprints could be a diagnostically useful method in the assessment of mucinous ovarian tumors.
The Value of Cytology in the Diagnosis of Ophtalmic Lesions Ostojic, Damjana Versa; Rubeša-Mihaljević, Roberta; Dinter, Morana ...
Journal of the American Society of Cytopathology JASC,
November-December 2022, 2022-11-00, Volume:
11, Issue:
6
Journal Article
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
. Papa-test je najbolji morfološki test probira za rak koji pomoću analize citologije vrata maternice otkriva predstadije i rane stadije raka vrata maternice. U Hrvatskoj se koristi u okviru ...oportunističkog probira, a od 1. 12. 2012. u organiziranom nacionalnom probiru. U svrhu klasifikacije i standardizacije citoloških nalaza vrata maternice u cijeloj Hrvatskoj koristi se modifikacija Bethesda klasifikacije. Obrazac sadrži kliničke podatke o pacijentici koje ispunjava ginekolog i citološki nalaz koji na osnovi analize Papa-testa pod svjetlosnim mikroskopom izdaje klinički citolog. U ovom preglednom radu opisuju se citomorfološke osobine abnormalnih pločastih i cilindričnih stanica vrata maternice te njihov klinički značaj. Zbog dokazane povezanosti humanog papiloma-virusa (HPV) s rakom vrata maternice sve češće se detekcija visokorizičnog HPV-a uvodi u probir za rak vrata maternice. U novije vrijeme metode temeljene na biološkim biljezima primjenjuju se na citološkim uzorcima u svrhu poboljšanja osjetljivosti i specifičnosti citologije u otkrivanju lezija visokog stupnja
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