Katsuhiko Hasumi

Microdissection Is Essential for Gene Expression Profiling of Clinically Resected Cancer Tissues

The gene expression array method enables us to achieve expression profiling with thousands of genes. Clinically resected bulk cancer tissues, however, contain not only cancer cells but also stromal cells, which may affect gene expression profiling and hamper accurate analysis of the cancer cells per se. Therefore, a procedure for dissecting specific cells, such as laser capture microdissection, is neededfor the clinical application of a gene expression array. There has been no study actually comparing 2 gene expression profiles, one obtained using RNA extractedfrom cancer cells by laser capture microdissection and one obtained using RNA extractedfrom bulk cancer tissues. Wefirst demonstrated the difference in expression patterns between them, without any amplification procedures. In addition, differential expression analysis between tumor and nontumor tissue yielded quite different patterns between the 2 methods. We conclude that microdissection is essential for gene expression profiling of clinical specimens.

Genetic Aberrations Detected by Comparative Genomic Hybridization in Ovarian Clear Cell Adenocarcinomas

Genetic abnormalities were detected by comparative genomic hybridization (CGH) in 12 ovarian clear cell adenocarcinomas. DNA sequence copy number abnormalities (CNAs) occurring in more than 20% of the cancers included increased copy numbers of 8q11-q13, 8q21-q22, 8q23, 8q24-qter, 17q25-qter, 20q13-qter and 21q22-qter and reduced copy numbers of 19p. Increases in copy numbers of 8q11-q13, 8q21-q22, 8q23 and 8q24-qter occurred more frequently in disease-free patients than in recurrent/non-surviving patients (p < 0.05). However, increases in copy numbers of 17q25-qter and 20q13-qter occurred more frequently in recurrent/non-surviving patients than in disease-free patients (p < 0.05). Furthermore, increases in copy numbers of 17q25-qter and 20q13-qter occurred together (p < 0.05). Additionally, there were negative correlations between increases in copy numbers of 8q21-q22 and 17q25-qter, and between 8q21-q22 and 20q13-qter (p < 0.05). It appears that ovarian clear cell adenocarcinomas can be classified into two subtypes, one being cancer with an increase in copy numbers of 8q and the other being cancer with increases in copy numbers of 17q25-qter and 20q13-qter.

Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion

Objective To analyze the incidence of pelvic lymph node metastasis in endometrial carcinoma with no myometrial invasion. Methods Between 1971 and 1995, 684 women with stage I endometrial carcinoma underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. The incidence of pelvic lymph node metastases in 100 cases without myometrial invasion was examined. Results Histologic examination of the surgical specimens revealed a single pelvic lymph node metastasis in each of four cases. The incidence of pelvic lymph node metastasis was four of 83 in grade 1, zero of 13 in grade 2, and zero of four in grade 3 tumors. Conclusion Pelvic lymph node metastasis in endometrial cancer with no myometrial invasion is not rare, even with grade 1 tumors. Lymphadenectomies may be necessary in all patients with endometrial cancer, except when clinical or operative factors increase the procedures risk of morbidity.

The Behavior of Endometrial Hyperplasia: A Prospective Study

Objective: To clarify the behavior of endometrial hyperplasia in a prospective study.

Treatment of squamous cell carcinoma of the uterine cervix with radiation therapy alone: long-term survival, late complications, and incidence of second cancers.

The objective of this retrospective study was to determine the survival rate, incidence of late complications, and incidence of second cancers when radiation therapy alone is used for carcinoma of the uterine cervix. Between 1971 and 1995, 1495 patients with squamous cell carcinoma of the uterine cervix (stages I–IV) were treated with radiation therapy alone in our hospital. Radiation therapy consisted of a combination of high-dose-rate intracavitary brachytherapy and external beam radiotherapy. The cumulative 5-year survival rates for stages Ib, II, and III/IVa carcinoma were 93.5, 77.0, and 60.3%, respectively, and the 10-year survival rates were 90.9, 74.5, and 56.1%, respectively. Local control rates for stages Ib, II, and III/IVa carcinoma were 92.0, 79.4 and 64.2%, respectively. Eighty-two (5.5%) patients suffered grade III/IV or V (fatal) complications. A second cancer developed in 13 (0.87%) patients. Second cancers were observed most frequently in the rectum (five cases), colon (three cases), and uterine body (two cases). Long-term follow-up data revealed that our method of radiation therapy alone for locally advanced carcinoma of the uterine cervix is effective, with low incidences of late complications and second cancers.

Malignant potential of positive peritoneal cytology in endometrial cancer.

Objective To investigate the malignant potential of positive peritoneal cytology in endometrial cancer. Methods Fifty patients with clinical stage I–II endometrial cancer in whom the disease was completely surgically resected and positive peritoneal smears were found at surgery formed the study population. In these patients, a tube for cytologic analyses was inserted into the peritoneal cavity when closing the abdomen. The peritoneal cavity was irrigated with physiologic saline, and washings were obtained through the tube 7 and 14 days after the operation. Results Persistence of positive peritoneal cytology was observed in four of seven patients with adnexal metastasis, zero of nine patients with nodal disease, and one of 34 patients with disease confined to the uterus, for a total of 10% (5 of 50). In the remaining 45 (90%) patients, no malignant cells were found in any of the washings. Conclusion The current series suggests that endometrial cancer cells found in the peritoneal cavity usually disappear within a short time and seem to have a low malignant potential. It also seems that only malignant cells from special cases, such as adnexal metastasis, may be capable of independent growth, and are possibly associated with intraperitoneal recurrence.

Effective chemotherapy consisting of bleomycin, vincristine, mitomycin C, and cisplatin (BOMP) for a patient with inoperable vulvar cancer

Combination chemotherapy consisting of bleomycin, vincristine, mitomycin C, and cisplatin (BOMP) was first applied to an inoperable case (57-year-old) with FIGO stage IV (T3N3 + M1B) squamous cell carcinoma of the vulva. After three courses of BOMP therapy, the patient achieved a complete response with few toxic effects and subsequently could undergo radical vulvectomy with bilateral inguinal and pelvic lymphadenectomy. On microscopic examination, only a minute focus of viable squamous cell carcinoma was observed in the vulvar lesion and regional lymph nodes, which was surrounded by fibrotic or necrotic tissues. The patient received a further two courses of BOMP as postoperative chemotherapy. Five courses of BOMP were extremely tolerable and did not require special care. She has been free of disease for 20 months and her present performance status is 0. The encouraging result warrants the use of this combination chemotherapy regimen in other patients with advanced squamous cell carcinoma of the vulva.

Early invasive cervical adenocarcinoma: its potential for nodal metastasis or recurrence

Objective To investigate the potential for nodal spread or recurrence in patients with early invasive cervical adenocarcinoma. The possible application of the International Federation of Gynecology and Obstetrics (FIGO) classification (1994) to this variant was also examined.

Effects of Ipriflavone on Bone Loss Following a Bilateral Ovariectomy and Menopause: A Randomized Placebo-Controlled Study

A randomized placebo controlled study was undertaken to evaluate the effect of ipriflavone (IP) against the bone loss in premenopausal ovariectomized women and postmenopausal women. Thirty-seven Japanese women who underwent premenopausal bilateral ovariectomy within 3 months (early stage group) and 52 Japanese women who were ovariectomized or who had undergone menopause more than 3 years before the start of the study (late stage group) were enrolled. The patients were randomly allocated into two groups: those who received IP (600 mg/day) and those who received placebo. The bone mineral density (BMD) of the lumbar vertebrae was measured by dual energy X-ray absorptiometry, and the markers of bone metabolism were measured at the same time that BMD was measured. In the early stage group, the IP group showed a 6.7% decrease in BMD from baseline levels, whereas the placebo group showed a 10.7% decrease (P > 0.01) at 12 months of treatment, and 7.1% and 12.6% decrease at 24 months of treatment, respectively (P > 0.01). In the late stage group, there was a 0.3% increase in BMD in the IP group and a 2.3% decrease in the placebo group at 6 months of treatment (P > 0.01), and similar changes were seen at 18 months (1.4% increase and 3.9% decrease; P > 0.01). IP suppressed bone loss compared with placebo, however, did not prevent acute bone loss in the early stage following ovariectomy. The effect of IP alone on bone loss in the early stage is not sufficient to reduce the risk of osteoporosis in later life.

Clinical study of primary carcinoma of the fallopian tube: Experience with 15 cases

Between 1950 and 1986, fifteen cases of primary carcinoma of the fallopian tube were diagnosed and treated at the Cancer Institute Hospital, Tokyo. These cases constituted 0.14% of the total number of gynecologic malignancies at the hospital during that period. The average age of the 15 patients was 55.7 years. The most frequent symptom was atypical genital bleeding, seen in 12 cases (80%). Massive watery discharge was seen in 4 cases (27%). In preoperative cytologic examination, 6 cases (40%) were positive for cancer. All cases underwent operation as therapy. Postoperative irradiation, adjuvant chemotherapy, and/or second- or third-look operations were also performed. Histopathologically, all materials were found to be adenocarcinoma. Four cases were well differentiated, eight were moderately differentiated, and three were poorly differentiated. As for the prognosis, 7 patients were followed more than 5 years postoperatively. The 5-year survival rate was 57% (4/7). In stage I cancers, the 5-year survival rate was 80% (4/5). The prognosis of stage I cancer patients was estimated to be rather good.