Cervical Malignant Tumors Research Articles

Pathology of Cervical Cancer

Squamous cell carcinoma is the most common malignant cervical tumor, but the incidence of adenocarcinomas has been rising during the past few decades. This article discusses the epidemiology and pathogenesis of the squamous cell carcinoma, its clinical and histologic features, including microinvasive carcinoma, its histologic grade, and variant tumors. The prognostic impact of these features and the differential diagnosis are also covered. The second portion of this article is devoted to the glandular tumors of the cervix, including adenocarcinoma in situ and invasive adenocarcinoma and its variants. The differential diagnosis of these tumors with tumor like glandular lesions is given special attention. Finally, less common malignant cervical tumors are covered, with an emphasis being placed on their significance.

Diagnostic value of high-resolution B-mode and power-mode sonography in the follow-up of thyroid cancer

Objective: Ultrasonography is an established diagnostic modality in the follow-up of thyroid cancer. Color flow Doppler has been proposed by some authors as an additional tool for differentiating benign from malignant cervical lesions in various types of head and neck cancer. Over the last few years, a new generation of high-resolution ultrasound platforms with the ‘power-mode’ feature has become available, that also enables the imaging of small vessel blood flow. The objective of our study was to find ways of optimizing the differentiation of benign and malignant cervical tumors in thyroid cancer follow-up by means of sonography. Methods: Hundred and twelve cervical lesions in 90 patients with thyroid cancer were evaluated by high-end ultrasonography (Sonoline™ Elegra, Siemens) using a small-part transducer (7.5 L 40, Siemens). B-mode sonography was performed at a frequency of 8 MHz. The Solbiati index (SI= ratio of largest to smallest diameter), configuration, echogenicity, intranodular structures, and margins were assessed. Perinodular and intranodular blood flow was evaluated by color flow Doppler (PRF 1250 Hz for conventional color flow Doppler, 868 Hz for power-mode Doppler). Possible malignancy was validated by histology, cytology, scintigraphy, and follow-up. Thirty five lesions were benign (diameter 0.4–3.0 cm) and 77 were malignant (0.4–5.4 cm). The patients were randomized into a test group and a learning group to determine the diagnostic value of various ultrasound criteria by means of statistical analysis. In the learning group, decision rules based on the dichotomized criteria were developed using a logistic regression model. Sensitivity and specificity of these decision rules were then evaluated in the test group. Results: The presence of an echocomplex pattern or irregular hyperechoic small intranodular structures (criterion A) and the presence of an irregular diffuse intranodular blood flow (criterion B) are the best indicators of malignancy, whereas an SI≫2 is highly indicative of benign changes. Color flow Doppler is a useful addition to B-mode scanning for distinguishing benign and malignant neoplasms in the follow-up of thyroid cancer. Power-mode Doppler sonography significantly improves imaging of perinodular and intranodular blood flow when compared with conventional color flow Doppler. Conclusion: We propose the following decision rules based on a combination of the criteria above: (A) and (B) fulfilled: malignant, if SI≤4; (B) but not (A) fulfilled: malignant, if SI≤3; (A) but not (B) fulfilled: malignant, if SI≤2; neither (A) nor (B) fulfilled: malignant, if SI≈1 (sensitivity: 90%; specificity: 82%; accuracy 88%).

Immunohistochemical Localization And Monoclonal Antibodies Quantitative Measurement Of Carcinoembryonic Antigen (CEA) In Cervical Neoplasia

Objective: To evaluate the significance of including CEA in serum and tissues in the management protocol of patients with cervical malignancies. Methods: The study included 68 patients divided into three groups :Group A:20 patients with malignant cervical tumors; Group B: 12 patients with benign cervical lesions, Group C: 36 women without any gynaecologic disorder. Serum level of CEA was measured prior to treatment and following therapy. Formalin fixed and paraffin embedded tissue blocks taken from 2 different sites were prepared. Immunohistochemical staining for CEA was performed. Results: The mean pre-treatment serum CEA values and the mean difference in serum levels were significantly higher in malignant cervical lesion. The mean pre-treatment serum CEA levels were significantly higher in positively stained lesions. The mean pre-treatment serum CEA levels was significantly higher in positively stained cases of squamous cell carcinomas The mean serum CEA Values before treatment were significantly higher in positively stained carcinomas in stage IIa (P 0.049).The mean difference between preand post-treatment serum CEA was significantly higher in positively stained carcinomas in stage IIa (P 0.01). the mean difference in serum CEA levels was significantly higher in stage IIb in comparison with stage I. In conclusion: immunohistochemical identification of CEA in tumor tissue and monoclonal antibodies quantitative measurement of CEA in human serum may be a useful adjunct in the management protocol of patients with cervical malignancies.

Correlation of human papillomavirus 16 and 18 with cervical neoplasia in histological typing and clinical stage in Taiwan: an in-situ polymerase chain reaction approach.

In situ polymerase chain reaction (ISPCR) promises to considerably enhance our ability to detect a few copies of target nucleic acid sequences in fixed tissues and cells. The aim of this study was to investigate cervical carcinoma to determine the human papillomavirus (HPV) types on paraffin-embedded tissue sections by ISPCR and standard in situ hybridization. The results will correlate the morphological characteristics of lesions with viral typing results. This study examined prevalence of HPV 16 and 18 DNA in biopsies from 85 cervical cancer patients by ISPCR, employing HPV 16, 18 consensus primers. There are 45 patients with squamous cell carcinomas, 13 with adenocarcinoma, 2 with adenosquamous carcinomas, 3 with small cell carcinomas, and 22 carcinoma in situ. The relation between the types of HPV detected, tumor type, and clinical stage were analyzed. Fifty-two of 85 biopsies were HPV 16- or 18-positive, HPV 16 being the most prevalent type. Squamous cell carcinoma had a high prevalence of HPV 16 and adenocarcinoma had a high prevalence of HPV 18. HPV 18 was the predominant type among high clinical stage (III-IV) cases while HPV 16 and mixed HPV 16 with HPV18 were significantly correlated with low clinical stage (0-I-II). Our results indicate that certain malignant cervical tumor phenotypes and stages correlate with specific HPV type, and that ISPCR is a sensitive and fast method to detect HPV in these patients.

Cervical tumor characterization by transvaginal color flow Doppler ultrasound.

The aim of the study was to investigate the blood flow characteristics of benign cervical lesions and invasive cervical tumors and to determine if invasive cervical tumors can be predicted by transvaginal sonography (TVS) and color flow Doppler (CFD). The study design incorporated an open prospective collection of data from patients attending the Women's Cancer Center, University of Minnesota and the Sydney Women's Cancer Center. Inclusion criteria included patients with known benign or malignant cervical pathology. The study group of 66 patients comprised 32 patients with invasive cervical cancer and 34 patients with benign cervical lesions. Benign cervixes were significantly more likely to have absent or normal flow whereas malignant lesions were significantly more likely to have abnormal or increased flow (P < 0.0001). No differences in the uterine or intratumor systolic, diastolic, or mean velocity were found between the two groups. A reduction in the uterine artery pulsatility index (PI) and resistance index (RI) from 1.84 to 1.55 and 0.73 to 0.71, respectively, and also in the intracervical PI from 1.5 to 1.1, in the benign compared to invasive group was found, none of which reached statistical significance. However the intracervical RI was statistically lower (0.62) in malignant tumors compared to patients with benign lesions (0.71) (P = 0.03). The effect of menopause on blood flow characteristics was variable and overall not significant. While the uterine artery systolic velocity was significantly higher in premenopausal women, no such effect was found for the diastolic or mean velocity or the PI and RI. In postmenopausal women, the intratumor PI and RI were higher compared to premenopausal women. In conclusion, transvaginal CFD analysis of the uterine arterial or intratumor bed does not appear to be beneficial in attempting to distinguish benign from malignant cervical tumors.

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原発巣不明頚部悪性腫ようの画像診断

The region of the HPV E7 oncoprotein homologous to adenovirus E1a and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation.

Some genital human papillomavirus (HPV) types, such as 16 and 18, are highly associated with malignant cervical tumors while others, such as HPV 6, are only rarely found in these malignancies. The E7 oncoproteins of HPV 6, 16 and 18 each have a 17 amino acid region with striking homology to adenovirus E1a and SV40 LT. E1a, LT and the E7 oncoprotein of HPV16 all bind the cellular Rb protein in vitro, and for E1a and LT this region of homology contains sequences essential for interaction with Rb. We have now found that in HPV 16 E7 this region (amino acids 21-37) contains two separate biochemical activities, each of which contributes to E7-mediated transformation. Rb binding was localized to the N terminus of this region, while the C terminus was shown to serve as a substrate for casein kinase (CK) II, which phosphorylated serine-31 and serine-32. Replacement of the two serines by non-phosphorylatable amino acids led to a reduction in transforming activity and abolished phosphorylation but did not affect Rb binding. Rb binding and CK II phosphorylation were also examined for the E7 proteins of HPV 6 and HPV 18. HPV 16 and 18 E7 bound similar amounts of Rb, but HPV 6 E7 consistently bound less. Phosphorylation rates also varied, with HPV 18 E7 being 2-fold faster than HPV 16 E7, which in turn was 2-fold faster than HPV 6 E7. We conclude that Rb binding and phosphorylation of E7 by CKII are independent activities which are required for efficient transformation by E7 and that these activities correlate directly with the relative oncogenic potential of these viruses.