High level expression of fms proto-oncogene mRNA is observed in clinically aggressive human endometrial adenocarcinomas

Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.     

Radiation treatment of FIGO stage IVA carcinoma of the cervix

Forty-eight patients with FIGO stage IVA cervix cancer were treated with radiation therapy at the Hunter Radiation Therapy Center, Yale--New Haven Hospital from 1966 to 1985. Nine of the 48 patients are alive without recurrence (NED) and the 5-year actuarial survival rate is 18% (+/- 6%, standard error). There was a substantial difference in outcome based on treatment technique. Thirty-five patients were treated with external beam (EB) plus intracavitary (IC) and 8 of these patients (23%) are NED. None of the 12 patients treated with EB alone are alive. One patient treated with preoperative EB plus exenteration is NED. The severe complication rate was 22% and most complications were vesicovaginal fistulas due to successful treatment for bladder involvement. There was a significant difference in survival for patients with minimal parametrial disease (stage IVA1) versus patients with significant parametrial disease (stage IVA2) which was defined as fixation to one or both pelvic sidewalls or hydronephrosis on IVP. The 5-year survival for stage IVA1 disease was 46% (+/- 14%) versus only 5% (+/- 4%) for stage IVA2 disease. Our results indicate that superior survival for stage IVA cervix cancer patients is associated with two factors: minimal parametrial disease and radiation treatment which combines EB plus IC.     

Immediate versus delayed hysterectomy for endometrial carcinoma: surgical morbidity and hospital stay

Presented is a retrospective review of the intraoperative complications, postoperative morbidity, and length of hospitalization in 138 patients with stage I endometrial carcinoma treated at Yale-New Haven Hospital from January 1, 1977 to December 31, 1981. One group (stage IA, grade 1) was treated with surgery alone; two groups were treated with preoperative intracavitary radium, followed with either an immediate or a delayed hysterectomy. The three groups were comparable in age, weight, and major preoperative medical problems. The mean estimated blood loss during surgery and transfusion requirements during hospitalization were similar for all three groups. The duration of the surgery in the immediate group was longer than the other two groups. The occurrence of febrile morbidity and major postoperative complications in the three groups was similar, except for bacteriuria, which was significantly more common in the immediate group. The length of the postoperative hospitalization was the same for each group; however, the delayed group as compared with the immediate group had a total hospitalization of two days longer. Hence, in the current study, immediate hysterectomy did not significantly increase the surgical or postoperative morbidity rate, compared with delayed hysterectomy. The single hospital stay in the former treatment group represented cost containment.     

Are cytosol estrogen and progestin receptors of prognostic significance in the management of epithelial ovarian cancers?

Cystosol estrogen and progestin receptor levels in tumor samples from 101 patients with previously untreated primary epithelial ovarian cancers were correlated with patient survival. Patients with stage I and II disease whose tumors contained elevated levels of cytosol progestin receptors had an improved survival over patients with tumors containing low levels of cytosol progestin receptors. However, patients with advanced ovarian cancers and low cytosol progestin receptors had significantly longer survival. The four-year estimated duration of survival with advanced disease and cytosol progestin receptors less than seven was 82%, whereas if the cytosol progestin receptors were seven or more, the four-year estimated duration of survival was only 10%. The explanation for this dichotomy is not evident at this time. In this study cytosol estrogen receptor levels were not associated with survival. These results suggest that measurement of cytosol progestin receptors is of prognostic value in advanced epithelial ovarian cancers.     

Borderline ovarian tumors

Ninety-four patients with borderline ovarian tumors were retrospectively analyzed for clinical features, treatments, and survival characteristics. There were 46 patients with FIGO stage IA cancer, 7 with stage IB, 20 with stage IC, 4 with stage IIB, 5 with stage IIC, 5 with stage IIIA, 3 with stage IIIB, and 4 with stage IIIC tumors. Seventy patients had at least a total abdominal hysterectomy and bilateral salpingo-oophorectomy, 20 patients had conservative surgery including unilateral salpingo-oophorectomy or ovarian cystectomy, and 4 patients had bilateral salpingo-oophorectomy. Fifteen patients with stage I disease received adjuvant melphalan therapy and 2 received external beam radiation for concomitant gynecologic cancers; 7 with stage II tumors received adjuvant melphalan therapy and 1 received external beam radiation; and 5 with stage III tumors received melphalan therapy and 6 patients received cisplatin-based combination chemotherapy. Follow-up ranged from 1 to 117 months, with a median of 33.5 months. Eighty-seven patients were alive. Seven patients died, two of disease. The overall 5-year survival rate was 83.0%; those treated with adjuvant therapy had a 79.5% survival, whereas the others had 84.6% survival. Second-look surgery was performed in 10 patients; six results were negative after melphalan therapy, one was negative after cisplatin combination therapy, and one was negative after no adjuvant treatment. Two patients had positive second-look surgery, one with stage IIIC disease treated with a cisplatin combination and the other with stage IC disease treated with melphalan. This review did not demonstrate that patients with borderline ovarian tumors benefited from adjuvant therapy.     

Estrogen and progestin receptor levels as prognosticators for survival in endometrial cancer

The survival of 213 postmenopausal patients with primary endometrial cancer was analyzed as a function of clinicopathologic features and cytosol steroid receptor levels. Estrogen receptor (ER) levels (P = 0.008) and progestin receptor (PR) levels (P = 0.0001) were negatively correlated with grade. ER and PR levels were positively correlated with each other (P = 0.0001), but neither was correlated with age. In 187 patients with stages I and II, ER positivity (greater than or equal to 20 fmole/mg cytosol protein (cp] was statistically associated with grade (P = 0.007); and PR (greater than or equal to 7 fmole/mg cp) was statistically associated with grade (P = 0.001). Univariant analysis revealed that survival for the early endometrial cancer patients was significantly dependent upon ER status (P = 0.0003), PR status (P = 0.0016), and grade (P = 0.0002). Multivariant analysis of ER status, PR status, age, and grade showed that the ER status was a significant prognostic factor for survival (P = 0.0168), even if the positivity of the PR status was defined at greater than or equal to 50 fmole/mg cp. If ER status was divided at 0-19, 20-100, and greater than 100 fmole/mg cp, survival was significantly different between the low range group and the other two groups. If PR status was divided at 0-6, 7-50, and greater than 50 fmole/mg cp survival was significantly different between the first two groups and the high range group. Thus, survival in these endometrial cancer patients was better predicted by ER status than grade.