Tsuneo Fujii

Koilocytotic lesions of the cervix. The relationship of mitotic abnormalities to the presence of papillomavirus antigens and nuclear DNA content.

It has been reported that abnormal mitotic figures (AMFs) occur principally in aneuploid lesions and that aneuploidy is a diagnostic feature of non‐endocrine‐dependent epithelial cancer precursors and cancers. Recently, AMFs have been reported in cervical lesions interpreted as flat condylomata, and it has been suggested by several authors that AMFs may not be diagnostic or aneuploidy or neoplasia, particularly in human papillomavirus‐(HPV)‐induced lesions. Although it is conceivable that AMFs may be a regular feature of HPV infection, their association with cytologic atypia and their presence in higher grades of cervical intraepithelial neoplasia (CIN) suggests that AMFs may herald the presence of a different lesion than the pure flat condyloma. In the current study, koilocytotic cervical lesions thought to be HPV‐induced were examined microscopically for the presence of AMFs, and the findings were correlated with the presence of HPV as determined by immunoperoxidase and nuclear DNA distribution patterns as measured by Feulgen microspectrophotometry. In unselected lesions originally diagnosed as flat cervical condylomata, AMFs were surprisingly common (22.6%), and did not correlate with the extent of koilocytosis. Immunoperoxidase (IMPO) stains were performed in 35 cases with AMFs, and were negative for HPV in 74.3% and positive in 22.8%. However, among the cases evaluated by IMPO, there was an inverse relationship between the presence of mitotic abnormalities and the expression of HPV antigen. Nine of 11 (81.8%) lesions containing AMFs were aneuploid, and 2 of 11 (18.2%) were polyploid. Abnormal mitotic figures have a range of morphology and frequency in koilocytotic cervical lesions. Although the biology of these lesions is not well‐defined, the presence of AMFs may identify a subgroup of HPV‐induced cervical atypias which represent a transition between flat cervical conylomata and CIN. Cancer 53:1081‐1087, 1984.

Histologic grade and karyotype of immature teratoma of the ovary

Seven cases of ovarian “pure” immature teratoma were encountered in patients 10 to 38 years of age, six cases being in Stage Ia and one case in Stage IIc. The primary tumors and recurrent growth observed in one case were histologically graded from 0 to 3 according to the criteria of Norris et al. Karyotypes of the tumors and the patients were determined using culture and banding techniques. The only nonsurviving case was in Stage IIc. Four primary tumors belonging to grades 0, 1, and 2 showed a normal 46, XX female karyotype and the patients are alive and healthy. Three grade 3 tumors showed various types of karyotype abnormalities (48, XX,+14,+21; 47, XX+20; 47, XXX). One patient died, one is alive after experiencing a recurrent tumor, and one has only been followed for 22 months. All seven patients had a normal 46, XX female chromosome constitution. Evidence to date indicates that karyotype of ovarian immature teratoma is either normal female 46, XX or a slight deviation from normal. It is postulated that in ovarian immature teratoma normal 46, XX karyotype is an indicator of favorable prognosis, whereas deviations in karyotype suggest a possibility of poor prognosis.

Cyclin E mRNA overexpression in epithelial ovarian cancers: inverse correlation with p53 protein accumulation.

Objective: We investigated the relationship between cyclin E mRNA overexpression and p53 protein accumulation in epithelial ovarian cancers. Methods: mRNA was isolated and cDNA was prepared from 36 epithelial ovarian tumors (three adenomas, three low malignant potential tumors, and 30 carcinomas), and six normal ovaries. The cyclin E mRNA expression levels relative to an internal control, β-tubulin, were determined by semiquantitative polymerase chain reaction (PCR). Cyclin E and p53 protein expression in ovarian cancer tissues were examined by immunohistochemistry using the same series of samples. Fisher exact test of significance and an unpaired t test were used for statistical analysis. Results: Considerable levels of cyclin E mRNA were detected in all normal ovaries and ovarian tumor samples examined by semiquantitative PCR amplification. mRNA levels of cyclin E were significantly higher in nine of 30 (30%) ovarian cancers compared with those in normal ovaries. The immunohistochemical expression of cyclin E protein was confirmed in the nuclei of tumor cells in 13 of 30 (43%) ovarian cancers. p53 protein accumulation was detected in 12 of 30 (40%) ovarian cancers examined. There was a significant inverse correlation between cyclin E mRNA overexpression and p53 protein accumulation (P <.01, Fisher exact test). Conclusions: Cyclin E mRNA overexpression frequently occurs in ovarian cancers without p53 protein accumulation. Cyclin E might have an important effect on the development of a limited number of ovarian cancers.

Recurrence of invasive cervical carcinoma more than 5 years after initial therapy.

OBJECTIVE To estimate the probability of and risk factors for the recurrence of invasive cervical carcinoma over 5 years after initial therapy. METHODS Patients (n = 827) with invasive cervical carcinoma were treated and received follow‐up care for up to 29 years. Late recurrence was defined as recurrence more than 5 years after initial therapy. The probability of late recurrence was evaluated in terms of clinical stage, histologic type, and type of initial therapy. RESULTS Late recurrence was seen in 21 of 569 patients who had survived 5 years (3.7%). Recurrence rates were 1.8% (six of 331) in stage I, 5.2% (eight of 154) in stage II, 8.6% (seven of 81) in stage III, and 0% (none of three) in stage IV. The probability of late recurrence in patients with stage I disease was significantly lower than that in stage II and stage III diseases (stage I compared with stage II, P = .038, stage I compared with stage III, P = .002). Late recurrence occurred in 21 (3.8%) of 547 cases of squamous cell carcinoma, whereas no late recurrences were found in 22 cases of adenocarcinoma. The late recurrence rate in patients who received radiation (7.1%, 17 of 241) was significantly higher than that in patients who received surgery (1.2%, four of 328; P = .001). CONCLUSION Patients with uterine cervical squamous cell carcinoma, especially those with stage II or stage III diseases who received radiation therapy as initial treatment, warrant annual follow‐up care beyond the standard 5 years after initial therapy.

Are DNA ploidy and epidermal growth factor receptor prognostic factors for untreated ovarian cancer? A prospective study.

&NA; To identify prognostic factors for untreated ovarian cancer, DNA ploidy, proliferative index (P.I.) and epidermal growth factor receptor (EGFR) expression were analyzed in a prospective series of 40 patients with ovarian cancer and 7 patients with borderline malignant ovarian tumor followed up for 5 years or more (median, 77 months). The frequency of aneuploid cells was 53.8% (21/39) in ovarian cancer and 14.3% (1/7) in borderline malignancy. There was no significant association between DNA ploidy and the clinicopathologic findings, in which aneuploid ovarian cancer was more common among advanced tumors. The S‐phase fraction and P.I. value were higher in the patients with aneuploid tumors (p = 0.076). EGFR expression was detected in 76.9% (30/39) of ovarian cancers and 42.9% (3/7) of borderline malignant ovarian tumors, and the mean EGFR level was 5.8 ± 12.1 (range: 0–49.5) and 28.3 ± 71.1 (range: 0–189.4) fmol/mg protein, respectively. There was no correlation between EGFR expression and DNA ploidy, P.I., and clinicopathologic findings analyzed. The 5‐year survival rate in patients with aneuploid tumors was significantly worse in patients with ovarian cancer (p = 0.0165, log‐rank test). No significant relationship was shown between P.I., EGFR expression, and 5‐year survival. Cox multivariate analysis showed that DNA ploidy, P.I., and EGFR expression are not associated with the risk of death (p = 0.5917, p = 0.9924, and p = 0.6840, respectively), although clinical stage shows a significant relationship (p = 0.0027). Our data showed that DNA ploidy is significantly related to the prognosis by univariate analysis, but DNA ploidy, P.I., and EGFR expression were not independent prognostic factors for the untreated ovarian cancer.