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The intention of the present study was to assess immunohistochemically the expression of c-erbB receptor family in cervical carcinoma specimens of young women. Simultaneously, HPV was detected in the same specimens using immunohistochemical assays. Seventy-five cervical intraepithelial and invasive cancer specimens were assessed retrospectively. Positive c-erbB-2 immunostaining was revealed in 11.7% of tumor specimens, while for c-erbB-3 and c-erbB-4 receptor the corresponding figures were 32% and 49.3%, respectively. Concerning HPV infection-markers, positive immunostaining was found in 31% of cases, while coilocytes were detected in 64% of patients. The correlation of c-erbB receptor expression with malignant aggressiveness in cervical cancer cells concurs with similar data regarding other neoplasias, thus rendering these receptors an important predictive factor and future therapeutic target.

In 1% to 3% of patients with cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VAIN) will either coexist or occur at a later date. The time interval from an earlier diagnosis of CIN 3 to a current diagnosis of VAIN 3 varies from two to 17 years. Invasive vaginal cancer occurred in a woman five years after total abdominal hysterectomy for cervical intraepithelial neoplasia. In women who have undergone total hysterectomy for cervical intraepithelial neoplasia or cervical cancer, postoperative cytologic and colposcopic follow-up of the vagina is necessary.

The aim of this study was to determine the optimal treatment policy in women presenting with an abnormal Pap smear showing low-grade squamous intraepithelial lesion (LGSIL), who additionally had normal colposcopic findings. We prospectively studied 160 women with LGSIL and normal colposcopy, and divided them into two groups. Group A, consisting of 54 women, was followed-up for a mean period of 42 months and had a new control smear 12 months after the initial one. Group B, consisting of 106 women, was followed-up for a mean period of 44 months and had two consecutive control smears (6 and 12 months after the initial), and a new colposcopy, depending on the findings. At the end of the first year, the lesion persisted in 37% and 39% of the patients in groups A and B, respectively. At the end of the study, regression or persistence of the LGSIL was revealed in 63% and 61% of the women in groups A and B, respectively. Aggravation of the lesions occurred after 16.5 and 15 months, respectively, in groups A and B. Our findings suggest that women with LGSIL and normal colposcopy do not need further therapeutic measures during the first year after the initial smear.

Regression rate of CIN 1 (LSIL) can reach 85%. The purpose of this study was to investigate retrospectively pathology specimens in CIN 1 cases who delayed treatment > 2 years despite the persistence of the lesion. One hundred and fifteen women diagnosed with CIN 1 were separated in two groups as follows: A) 92 women who underwent ablative treatment within three months after the completion of two years; B) 23 women who delayed ablative treatment for a mean interval of > 1 year after the completion of two years. Exclusion criteria were normal cytology and colposcopy results within the completion of two years. The chi-square, t-test and Kaplan-Meier method were used for analysis. Persistence of LSIL lesions was observed in 84% of the first group and persistence or regression of the lesion in 78% of the second one. The study suggests the possibility of prolongation of the observation period after LSIL diagnosis. Prospective studies with close follow-up are needed for final conclusions.

The aim of this study was to determine whether the clinical value of a second Pap smear during colposcopy outweighed its cost-effectiveness and reliability parameters. We studied retrospectively 569 cases focusing on A) The initial Pap smear, B) The smear performed during colposcopy, C) The colposcopic findings, and D) The histopathological reports of the cases where biopsy sampling was performed. In 380 patients (67%), the second Pap smear corresponded to the first one. In 13% of the patients, the cytological lesions were worse (particularly in 2% of the patients staging increased from HPV-associated reactive cellular changes to CIN II, or from CIN I to CIN III), and in 20% slighter than the initial. In 79% of the cases revealing more serious lesions in the second smear, the histological result of the biopsy corresponded to that of the initial smear. Conclusively, only 2% seem to benefit from a second repeat Pap smear during referral colposcopy.

Reduced expression of the metastasis suppressor gene nm23-H1 has been previously correlated with high tumor metastatic potential and fatal clinical outcome in several types of human carcinomas. The aim of the study was to identify the expression of nm23-H1 in a variety of premalignant and malignant cervical lesions. The study comprised 106 cervical biopsies obtained from 106 women ranging in age from 23 to 68 (median 42) years. Histologic slides stained with H&E were evaluated blindly by two pathologists and a consensus diagnosis was established for each case. In addition, immunohistochemical stain was employed and a monoclonal antibody against nm23-H1 (YLEM Rome, Italy) was used. Twenty-five of the cervical biopsies showed changes of mild dysplasia (CIN I), whereas 28 demonstrated features of moderate dysplasia (CIN II) and 28 severe dysplasia (CIN III). In 25 cases infiltrating squamous cell carcinoma was identified. Expression of nm23-H1 was evident in 9/25 (36%) CIN I, 13/28 (46%) CIN II, 22/28 (78.5%) CIN III and 17/25 (68%) infiltrating carcinoma biopsies. Statistically significant differences were observed between CIN II and CIN III (p=0.003), and CIN II and infiltrating carcinoma (p=0.002) groups. Expression of the nm23-H1 gene in premalignant and malignant cervical lesions indicates that this gene may play a substantial role in carcinogenesis and tumor progression.

Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly-differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis.

Angiogenesis has been extensively studied in several types of invasive carcinomas and has been correlated-with tumor growth and metastasis. In some of these studies it has been shown that angiogenesis preceeds neoplastic transformation. A correlation is evident between microvessel density and conditions that exist much before the onset of tumor formation (i.e. dysplastic lesions). In this study, tumor vascularity was quantified in a series of cervical lesions: 92 dysplasias (31 mild, 24 moderate and 36 severe) and 11 infiltrating squamous cell carcinomas. Microvessels were visualized by a polyclonal antibody against factor VIII-related antigen (DAKO), using a streptavidin-peroxidase immunohistochemical method. Vessel density was quantified in 3 high power fields (hpf) of the most vascular areas, by two independent observers. Mean vascular counts were 13 +/- 5 vessels per unit area in CIN I lesions, 17 +/- 4 in CIN II, 20 +/- 6 vessels in CIN III and 17 +/- 5 in infiltrating carcinomas. There was a progressive increase of vascularity in the dysplastic lesion in the samples with increasing atypia in relation to controls. No significant differences were noted between severe cervical dysplasias and infiltrating carcinomas. Our findings suggest that angiogenesis may be an important event in tumor initiation and the conversion of the normal epithelium into cancer.