Tsuyoshi Iwasaka

Successful Pregnancies in 2 Infertile Patients with Endometrial Adenocarcinoma

Two infertile patients with well-differentiated endometrial adenocarcinoma succeeded in having their own babies with assisted reproductive technology following treatment with a high dose of medroxyprogesterone acetate and repeated endometrial curettages. Their follow-up pathological examinations revealed no evidence of recurrent disease. Consequently, conservative treatment may be indicated in patients with well-differentiated endometrial adenocarcinoma at an early stage who desire to preserve their fertility.

Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia: a cohort study in Japan

One hundred and eighty-five Japanese women with cervical intraepithelial neoplasia (CIN) were enrolled in this follow-up study. On the basis of the prevalence of human papillomavirus (HPV) DNA in Japanese cervical cancer patients, HPV types were categorized into three groups as follows: (1) high risk (types 16, 18, 33, 52, and 58), (2) intermediate risk (types 31, 35, 39, 51, 56, 59, 68, and 70), (3) low risk (type 6, 30, 42, 53, 54, 55, 66 and unclassified types). High-risk HPV infection was a risk factor for progression of the disease. The regression rate in the HPV negative group was higher (83.3%) than those in the HPV positive groups, but the differences in regression were no longer significant after adjustment for age and CIN grade. It is also noted that a lower cytomegalovirus IgG level and a smaller number of past pregnancies might be associated with the regression of CIN lesions.

Endometrial carcinomas with lymph node involvement: novel histopathologic factors for predicting prognosis.

The purpose of this study was to evaluate the clinicopathologic prognostic factors of endometrial carcinoma with lymph node metastasis (stage IIIc) in 24 patients with endometrial carcinoma. Differences in survival rates were analyzed for each clinicopathologic factor. The ratio of lymph nodes containing metastatic tumor to dissected lymph nodes (metastatic ratio), invasion of tumor cells into perinodal fat, and the presence of desmoplasia were examined. No statistically significant differences in survival rates were observed between any of the histologic parameters of the primary tumors. Cases with a high metastatic ratio exhibited significantly lower survival rates. Cases without tumor invasion into perinodal fat had significantly longer survival compared with cases with invasion. Cases without desmoplasia in the positive lymph nodes had significantly longer survival than cases with desmoplasia. The number of positive lymph nodes, desmoplasia in the lymph nodes, and invasion into perinodal fat are the most important prognostic factors in stage IIIc endometrial carcinoma.

Retinoic acid and interferon-α effects on cell growth and differentiation in cervical carcinoma cell lines

OBJECTIVE To investigate and compare the efficacy of all‐trans retinoic acid (RA) and/or interferon‐α (IFN‐α) on premalignant and malignant models of cervical cancer. METHODS Cell growth rate was examined after treatment for 4, 7, and 10 days with RA and/or IFN‐α of human papillomavirus type 18 (HPV 18)‐immortalized endo‐ and ectocervical cells, nontransformed serum‐adapted cells, transformed cells, three adenocarcinoma, and three squamous cell carcinoma cell lines. The effect on epithelial differentiation by RA and IFN‐α was examined in organotypic culture. Induction of apoptosis was examined by modified terminal transferase‐mediated deoxyuridine triphosphate‐biotin nick end‐labeling (TUNEL) and DNA fragmentation. RESULTS Cell growth rate was inhibited by RA, 84–96% in HPV 18‐immortalized endocervical cells, SiHa, and ME180, 0% in OMC‐4, and 18–62% in other cell lines; and by IFN‐α about 75% in SiHa and ME180 and 14–40% in the other cell lines. Combining RA and IFN‐α increased the antiproliferative effect in premalignant cell lines and some cancer cell lines except OMC‐4, SiHa, and HT‐3. In rafts, RA treatment reversed human endocervical cell metaplasia and HPV 18‐immortalized endo‐ and ectocervical cell dysplastic epithelial differentiation. Interferon‐α, not RA, treatment of HPV 18‐immortalized endo‐ and ectocervical cells induced apoptosis. CONCLUSION Cell growth inhibition by treatment with RA, IFN‐α, and their combination differentially depends on treatment type and time, cell origin, cell line, and oncogenic state. In a premalignant model of cervical carcinoma, RA reduces dysplastic differentiation and IFN‐α induces apoptosis. These data confirm that these treatments may be effective for preventing or treating premalignant cervical lesions.

Analysis of Nuclear Chromatin Distribution in Cervical Glandular Abnormalities

OBJECTIVEnTo measure the intensity of hematoxylin staining for the analysis of chromatin distribution and to define a clear set of standards.nnnSTUDY DESIGNnCervical smears obtained from 12 patients with glandular lesions, 5 with squamous lesions and 3 without cervical lesions were used for NIH image analysis (public domain NIH image program developed at the U.S. National Institute of Health, available through the Internet by anonymous ftp from zippy.nimh.nih.gov or on floppy disk from the National Technical Information Service, Springfield, Virginia). In addition, the same cervical smears were restained with propidium iodide, and the DNA content in the nuclei was compared with that with hematoxylin staining.nnnRESULTSnChromatin distribution was categorized into 3 patterns. Pattern A was that for which the highest staining density was localized in the periphery of the nucleus, while in pattern C it was localized in the center of the nucleus. Pattern B was the intermediate type between patterns A and C. In patients with adenocarcinoma, pattern B was predominant; pattern C was also relatively frequent in this group. In atypical glandular cells observed in patients with squamous lesions, patterns A and B were predominant and pattern C rarely seen. Analysis of DNA content in the nucleus revealed that nuclei showing pattern B contained significantly higher quantities of DNA than those showing pattern A.nnnCONCLUSIONnNuclear chromatin distribution seems to correlate well with DNA content, and analysis of the chromatin distribution pattern is helpful for the diagnosis of cervical glandular neoplasia.

Ectopic chromosome around centrosome in metaphase cells as a marker of high-risk human papillomavirus-associated cervical intraepithelial neoplasias.

This report describes the appearance of ectopic chromosome around centrosome (ECAC) in metaphase cell nuclei of high‐risk HPV‐associated cervical neoplasms. ECAC are clearly visible on HE‐stained sections as a tiny (approx. 0.7 μ), round, dark structure or an aggregate of filamentous chromosome, often symmetrical at bilateral centrosomes. They appear in CINs from an early stage (CIN I), with the highest incidence in HPV16‐associated CIN II–III (75%), and are less common in HPV‐related invasive carcinomas (21%) and in lesions associated with high‐risk HPV types other than 16. Rates for ECAC‐positive nuclei in metaphase preparations (ECAC rate) for each lesion ranged 3.6–30%, the average being 14.5%. ECAC appeared very rarely in CINs associated with intermediate‐risk HPVs and was never encountered in HPV6/11‐induced condylomas or HPV‐unrelated neoplasms in other organs. ECAC may be morphologic evidence of HPV‐induced chromosomal instability working as a background mechanism in cervical carcinogenesis and also a useful marker for the histopathologic differentiation of high‐risk CINs.