Improved prediction of survival in advanced adenocarcinoma of the ovary by immunocytochemical analysis and the composition adjusted receptor level of the estrogen receptor.

Conventional cytosol estrogen receptor analysis is not a significant prognostic variable in serous ovarian carcinoma. Although the use of immunocytochemical receptor analysis for estrogen does provide prognostically useful information in enhanced accuracy of predicting survival in patients with ovarian cancer, its usefulness can still be improved. Surgical samples from ovarian carcinomas are heterogeneous in tissue composition. Immunocytochemical receptor analysis allows for the specific assessment of the tumorous portions of a histological specimen. However, it is limited by its dependence on staining intensity as the determining factor. Biochemical receptor analysis does provide objective information concerning the number of receptor molecules present in a given sample, but the value is not adjusted for histological composition of the tumor section. Therefore, we have attempted to combine the advantages of both methods. By adjusting the conventional receptor analysis for the percentage of tumor present in the specimen, we have eliminated the tissue heterogeneity as a confounding variable. The resulting value is named Composition Adjusted Receptor Level or CARL. A prospective study was performed on the estrogen receptor concentrations in 61 ovarian cancers. Minimum follow-up was 8 years. For the percentage of tumor in the specimen, a highly significant correlation of the assessment of the two pathologists was observed. Stage (P < 0.05) and grade (P < 0.05) as well as cell type (P < 0.05) were found to be significant prognostic variables. In an attempt to eliminate the confounding influences of these variables, the CARL of the estrogen receptor was assessed with regard to its prognostic significance in 32 grade 2 and 3 serous carcinomas of the ovary, stage III and IV. A linear correlation between CARL and survival was found above a threshold estrogen receptor concentration of 15 fmol/mg cytosol protein using a correlation of the Cox proportional hazards model (P < 0.02). Our data suggest that (a) the assessment of the percentage of tumor in a given sample is not significantly observer dependent, (b) CARL is a significant predictor of survival in serous ovarian carcinoma, and (c) a CARL should be determined for the analysis of any cytosol receptor in solid tumors.

Stage II endometrial carcinoma. Results and complications of a combined radiotherapeutic-surgical approach.

Since one third of the patients with Stage II endometrial carcinoma have occult extrauterine pelvic metastases at diagnosis, adequate treatment must include the pelvic lymph nodes and parametria. Eighty-three patients with Stage II endometrial carcinoma were treated between January 1964 and December 1983. Sixty-nine patients (83%) received combined whole-pelvic irradiation and surgery, five (6%) had surgery alone and nine (11%) had radiotherapy alone. Five-year actuarial survival rates were 67%, 60%, and 38%, respectively. No pelvic recurrence occurred in the 69 patients who received the combined therapy, and there was no vaginal recurrence in the 80 patients treated with intracavity radium. There was a significantly lower incidence of pelvic lymph node metastases (P = 0.03) in patients treated with preoperative irradiation. The median time to recurrence was 17 months, with 67% of the recurrences diagnosed before 2 years, and 88% within 5 years. Ten patients (12%) incurred severe complications and three died as a result. Whole-pelvic irradiation, intracavity radium, and hysterectomy are effective treatment for occult pelvic and vaginal disease.

The significance of residual tumor after preoperative pelvic irradiation for stage II endometrial carcinoma.

The prognostic significance of residual endometrial carcinoma in the hysterectomy specimen after preoperative radiotherapy is controversial. Sixty-two patients with stage II endometrial carcinoma were treated with a standardized program of preoperative radiotherapy, followed in six weeks by an extrafascial hysterectomy. Twenty patients (32%) had no residual carcinoma in their hysterectomy specimens and 42 (68%) had residual carcinoma. There were no significant clinical, surgical, or pathologic differences between patients with or without residual carcinoma. Patients with no residual carcinoma had a 25% recurrence rate and a 53% actuarial five-year survival rate. Patients with residual carcinoma had a 21% recurrence rate and a 78% actuarial five-year survival rate. The presence of residual endometrial carcinoma in the hysterectomy specimen does not imply a compromised prognosis in patients with stage II endometrial carcinoma treated by the described method.

Adenoid cystic carcinoma of the breast.

Twelve cases of pure adenoid cystic carcinoma of the breast were reviewed. Patients ranged in age from 34 to 69 years. Seven carcinomas were in the right breast, and five in the left; five of the 12 were located in the central region of the breast, five in the upper outer quadrant, and the two in the upper inner and lower inner quadrants, respectively. Average diameter of the primary tumors was 2.5 cm (range, 0.7 to 6.0). We graded the tumors according to a system used for adenoid cystic carcinoma of the salivary gland: five tumors were grade I, six were grade II, and one was grade III. An average of 5 years after diagnosis, all patients with grade I tumors were either alive without evidence of disease or had died of unrelated causes. Among the six patients with grade II tumors, one developed a local recurrence 5 years after diagnosis and subsequent pulmonary metastasis, and one died of metastatic adenoid cystic carcinoma 13 years after diagnosis. The one patient with grade III tumor had shown metastases in axillary lymph nodes at mastectomy, and she died of disease 2 years later. These findings suggest that the grading of adenoid cystic carcinoma of the breast may be important in prognosis and treatment selection.

Prognostic factors in stage II endometrial carcinoma.

The rarity of Stage II endometrial carcinoma and variable treatment modalities have made the evaluation of prognostic factors difficult. Clinical, surgical, and pathologic characteristics were evaluated in 64 patients treated with whole pelvic irradiation and intracavitary radium followed by hysterectomy at The University of Texas M.D. Anderson Hospital and Tumor Institute from January 1965 to December 1983. Comparison of 5-year actuarial survival rates revealed the following statistically significant categories: age, grade, depth of myometrial invasion, disease extent at surgery including lymph node metastases, and pelvic cytology. Race, weight, and cell type were not significant prognostic factors. Evaluation of prognostic factors at surgery includes pelvic and para-aortic lymph node biopsies, omental biopsy, pelvic cytologic washings, and biopsy of any suspicious tissues. Patients with adverse prognostic factors are candidates for trials with adjuvant therapy.

Proton NMR of human breast tumors: correlation with clinical prognostic parameters.

Proton NMR spectroscopy and imaging of human breast tissue have provided new methods in studying breast carcinomas. Continuous wave proton NMR spectroscopy in this study is able to discriminate breast carcinomas from normal breast tissue on the basis of the integrated area under the water and lipid peaks, width at half height of the water peak, and chemical shift of the lipid peak. In addition, the NMR parameters were correlated with the following clinical and pathologic prognostic indices: TNM tumor stage, nuclear grade, and estrogen receptor status (ER). Width at half height of the lipid peak (1/2 delta lipid) correlated with tumor content and ER. Studies using higher resolution proton or phosphorus NMR spectra may separate signals that can correlate with biological information on breast neoplasms useful to the clinician. Chemical shift of the lipid peak may be used to sharpen contrast on MRI of breast tumors.

Nature of cervical involvement in endometrial carcinoma.

In patients with endometrial carcinoma the prognostic significance of clinical and histopathologic variants of cervical involvement is unknown. Fifty-eight patients with endometrial carcinoma and cervical involvement diagnosed by gross examination or endocervical curettage are reviewed. Three clinicopathologic groups were identified: gross cervical involvement (10 patients), occult stromal invasion (25), and no evidence of stromal invasion (23). There were no differences in clinical, pathologic, surgical, or therapeutic characteristics. There was no significant difference in actuarial 5-year survival rates between patients with gross cervical involvement (70%) and occult disease (65%). There was also no significant difference in survival rates among patients with occult cervical stromal invasion (67%). The presence of cervical involvement in endometrial carcinoma is an important prognostic factor. However, the extent of cervical involvement does not appear to be of significant prognostic value.

Sarcomatoid carcinoma of the breast: an immunohistochemical study of six cases.

Six cases of sarcomatoid carcinoma of the breast (SCB) were studied with a panel of antibodies directed against epithelial and sarcomatoid components. The monoclonal antibodies (MoAb) AE-1/3, CAM 5.2, and CEA were used to detect epithelial differentiation; polyclonal antibodies against S-100 protein and MoAb against the intermediate filaments desmin and vimentin were used to detect mesenchymal differentiation in the sarcomatoid component. Six cases of invasive duct carcinoma (IDC) and two cases of cystosarcoma phyllodes (CP) were compared to SCB using the same panel of antibodies. In all three groups studied, the epithelial component in the majority of cases stained with anti-cytokeratin antibodies. S-100 protein antibodies stained the epithelial and sarcomatoid components in four cases of SCB; vimentin MoAb stained the epithelium in two cases and the sarcomatoid component in four cases of SCB, while MoAb CEA failed to stain any component of SCB. In contrast, the epithelium in five of six cases of IDC stained with CEA MoAb and only one of six stained for S-100 protein. Possible reasons for the discrepant immunohistochemical staining patterns among SCB, IDC and CP are discussed, in addition to the limitations and pitfalls of immunohistochemistry in diagnostic surgical pathology.

Prognosis in node-negative breast cancer.

In a selected group of 207 breast cancer patients with tumor-free axillary nodes, clinical and pathological features were evaluated as to their relationship to long-term disease-free survival. No clinical feature was found to be prognostically useful. Of pathologic features studied, four appear to have significance. These are the volume of the primary mass, the histologic or nuclear grade, the presence of invasive lobular carcinoma in the primary mass, and possibly the presence of neoplastic cells in intramammary lymphatic vessels. When two or more of these four features are present, prognosis is less favorable than when there is only one, but the influences are not arithmetically additive.

Correlation of estrogen receptor level and lipid staining in breast carcinoma.

Intracytoplasmic lipid was demonstrated in 10% or more of the cells in 13 (26%) of 50 estrogen receptor (ER)-positive breast carcinomas and in four (14.8%) of 27 ER-negative breast carcinomas. Thus, proportionately more positive tumors contained significant amounts of intracytoplasmic lipid. The difference, however, was not statistically significant. Furthermore, the presence of lipid as a test to predict the ER status is not useful because of its low efficiency and predictive value.

Carcinoma of the breast with pseudosarcomatous metaplasia.

Twenty-six cases of breast carcinoma demonstrating pseudosarcomatous metaplasia are described, and their clinical and pathologic aspects are correlated. The metaplastic elements include mature and immature bone, cartilage, myxoid stroma, loose fibromyxoid and dense spindle-cell stroma, and anaplastic stroma with giant cell features. Light and electron microscopic examination demonstrated an orderly sequence of transformation and dedifferentiation of epithelial cells to become undifferentiated mesenchymal cells. These tumors are more aggressive than purely epithelial carcinomas. The overall survival rate was 44%. Five-year survival figures for TNM Stages I, II, and III lesions were 56%, 26%, and 18%, respectively. The incidence of lymph node metastasis was 25% despite the large size of many of these tumors. Systemic metastases replicated the range of metaplastic elements seen in the primary site. Patients with tumors composed predominantly of pseudosarcomatous elements had worse prognoses than those with predominantly epithelial components (28% versus 62%, 5-year survival).

Pathologic types of breast cancer: their prognoses.

Mammary epithelium gives rise to a wide variety of histologically diverse carcinomas. Some types are associated with predictable patterns of clinical behavior, and it is important that these be recognized since, in many instances, therapeutic modifications are indicated. Among the kinds of breast carcinoma generally considered to have prognoses more favorable than average are adenoid cystic carcinoma, tubular carcinoma, juvenile secretory carcinoma, and perhaps medullary carcinoma with lymphoid stroma. Some of the prognostically unfavorable carcinomas are carcinoma with sarcomatoid metaplasia and inflammatory carcinoma. In applying this information to individual clinical situations, it is critical that a standard classification be consistently used and that its criteria be strictly observed. The 1981 edition of the classification promulgated by the World Health Organization while not flawless, is recommendable, since it includes both concise verbal definitions and admirably clear photomicrographs. Whatever the system of terminology chosen, it should be one equally acceptable to the pathologist responsible for histologic diagnosis and the physician responsible for treatment, and it should be clearly understood by both of them. These special types of carcinoma constitute only a minority of all breast cancers.

Estrogen and progesterone receptor titers in primary epithelial ovarian carcinomas.

Only 69% (42 of 61) of the documented ovarian tumor specimens received between September 1981 and August 1982 contained 75% or more viable tumor. Of the 42 measured for estrogen receptors (ER) and progesterone receptors (PR), 34 (81%) had estrogen-binding titers. greater than or equal to I fmol/mg of cytosol protein, while 18 (43%) had progesterone-binding titers greater than or equal to 5 fmol/mg of cytosol protein. ER and PR titers were found to be independent of histologic grade, clinical stage, patient age, age at first pregnancy, age at menarche, age at menopause and number of pregnancies. The presence of ER and PR in malignant ovarian tumors suggests that assays positive for these hormones could aid in the selection of patients suitable for hormonal therapy.

Mixed mesodermal sarcoma of the ovary. Treatment with combination radiation therapy and chemotherapy.

Twenty patients with mixed mesodermal sarcoma of the ovary treated at the M. D. Anderson Hospital and Tumor Institute in Houston, Texas are reviewed. This report focuses on 12 patients treated post-operatively with combination radiation therapy and chemotherapy with vincristine, dactinomycin, and cyclophosphamide (VAC). There were 4 patients achieving complete tumor control, including one who is alive without disease beyond 5 years and 3 who died of unrelated causes without disease at autopsy. One other patient had a significant disease-free interval of 18 months. Compared to previous reports, combination radiation and VAC chemotherapy appears effective in this disease. Due to the observed myelosuppression and gastrointestinal and neurologic toxicities, however, treatment modifications have been recommended.

Problems in the classification of breast cancer.

This article has sought to clarify the problems that beset the histologic classification of the numerous forms of breast cancer. Not only is classification itself difficult, but our lack of complete understanding of breast cancer often leaves us without criteria sufficiently clear to establish definite categories. Any adopted classification can be expected to require repeated revision as new information becomes available. Uniformly applying a classification will forever be hampered by factors inherent in the practice of surgical pathology and by the nature of breast disease. Considering the inherent problems, there is surprising uniformity among pathologists interested in the study of mammary carcinoma. The diversity is not so much an omen of impending chaos as a manifestation of a continuing struggle to understand the disease better.

Characterization of a cell line (SW756) derived from a human squamous carcinoma of the uterine cervix.

An established cell line, SW756, derived from a primary squamous carcinoma of the uterine cervix is described by its morphology, ultrastructure, karyotype, genetic signature analysis, HLA typing, and tumorigenesis in the nude mouse. Cultured cells obtained from the SW756 derived nude mouse tumor also were studied for chromosome and isozyme markers. The original tumor was poorly differentiated carcinoma with minimal keratinization and is compared with that occurring in the nude mouse after the cultured cells were inoculated. The nude mouse tumor showed similar histological features, but better differentiation than the original tumor. Karyotype analysis of SW756 demonstrated a hyperdiploid stem line number and several marker chromosomes (MI-M6). No HeLa marker chromosomes were identified. The isozyme pattern for SW756 reported by others has been confirmed. The unique chromosome and isozyme features have been identified repeatedly in the cultured cells and, most importantly, in the post nude mouse culture. We recommend SW756 as a defined human tumorigenic cell line derived from a primary squamous carcinoma of the uterine cervix.

Melanin-like pigment in the human prostate.

Twenty surgical specimens of prostate [1 histologically normal, 8 with benign hyperplasia (BPH), and 11 with cancer (PCa)] were examined by histochemical staining methods for the presence of a melanin-like pigment that we first observed in organ culture. Fontana-Masson-positive pigment was observed in epithelial cells of the normal specimen, of five BPH and of eight PCa. The distribution of pigment in BPH was unpredictable and patchy. The pigment was consistently absent in neoplastic epithelia. Silver-positive stromal cells also were observed in a number of the specimens. The epithelial pigment reacted to histochemical stains in part like melanin, in part like lipofuscin. It probably represents an endogenous pigment similar to other types of noncutaneous melanins.