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Biomedical subjects

Michael T Deavers

Publications and source records attributed to Michael T Deavers.

At least 19 recordsLinked to original sources

Activated SRC protein tyrosine kinase is overexpressed in late-stage human ovarian cancers.

OBJECTIVE: The objective of this study was to determine if the Src tyrosine kinase is overexpressed and activated in late-stage human ovarian cancers. METHODS: Western analysis and immune complex kinase assays were performed on a panel of human ovarian cancer cell lines and normal ovarian epithelial cell cultures, and immunohistochemical analysis for Src and activated Src were performed on a panel of late-stage human ovarian tumors. RESULTS AND CONCLUSIONS: Src is overexpressed and activated in a majority of late-stage ovarian tumors as well as in a panel of cultured malignant human ovarian epithelium grown in vitro, but not in normal ovarian epithelium (NOE) or immortalized NOE. Src overexpression was found to be frequently, but not always, associated with HER-2/neu overexpression, but no statistical association between Src and Her-2/neu overexpression could be demonstrated.

Enzyme Activation↗

Development of endometrial cancer after radiation treatment for cervical carcinoma.

OBJECTIVE: To detail the Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center experience with 23 patients treated with radiation therapy for invasive cervical carcinoma who subsequently developed endometrial carcinoma. METHODS: We conducted a retrospective chart and pathology review on patients diagnosed with endometrial cancer between 1976 and 2000 who had previously received definitive radiation treatment for cervical cancer. Abstracted data included patient demographics, type of radiation therapy, histological grade, histological subtype, and stage of endometrial cancer. RESULTS: The mean age at endometrial cancer diagnosis was 64.4 years (range 53-80), and the average latency period from initial therapy to development of endometrial carcinoma was 14 years (range 6-27). Distribution by stage, grade, and histology was as follows: stage I, five (22%); stage II, one (4%); stage III, nine (39%); stage IV, seven (30%); unknown stage, one (4%); grade 1, one (4%); grade 2, three (13%); grade 3, 17 (74%); unknown grade, two (9%); carcinosarcoma, eight (35%); endometrioid, four (17%); papillary serous, six (26%); clear cell, one (4%); mucinous, one (4%); undifferentiated, one (4%); and unknown histology, two (9%). The median survival was 24 months, and the 2- and 5-year survival rates were 50% (95% confidence interval [CI] 31.4%, 78.9%) and 21% (95% CI 8.1%, 56.3%), respectively. CONCLUSION: Patients treated with definitive radiation therapy for invasive cervical cancer may still have viable endometrium at risk for neoplasia. Endometrial cancers that develop after radiation treatment have a preponderance of high-risk histological subtypes and, consequently, a poor prognosis.

Adenocarcinoma↗

beta-catenin nuclear localization is associated with grade in ovarian serous carcinoma.

OBJECTIVE: beta-Catenin has been previously associated with oncogenic activity in human cancers. We evaluated whether beta-catenin also plays a role in papillary serous ovarian neoplasms. METHODS: Immunohistochemistry for beta-catenin was performed on the primary ovarian serous neoplasms of 105 women. Of these, 10 were low malignant potential (LMP) serous tumors, and 95 were serous cancers. Nuclear beta-catenin staining was correlated with grade of tumor and median survival. OVCAR-3, OVCA-420, OVCA-432, and MDAH-277-10c were evaluated for beta-catenin localization and transfected with a T-cell factor (TCF) responsive reporter to evaluate beta-catenin transcriptional activity. RESULTS: Of 105 serous tumors, 13 (12.3%) demonstrated beta-catenin nuclear staining. Eleven of 48 high-grade serous carcinomas (23.0%) demonstrated nuclear staining compared with 1 low-grade serous carcinoma (2.1%) (P = 0.006). One LMP tumor had nuclear staining. beta-Catenin nuclear localization was undetectable in the cell lines tested. Furthermore, transient transfection of the cell lines with a TCF-responsive reporter did not demonstrate significant constitutive transcriptional activation. CONCLUSIONS: We found a statistically significant correlation between beta-catenin nuclear localization and ovarian high-grade serous carcinomas. Thus, deregulation of beta-catenin may play a role in the pathogenesis of ovarian high-grade serous carcinomas in contrast to ovarian low-grade serous carcinomas and LMP serous tumors.

Adult↗

Overexpression of kallikrein 10 in epithelial ovarian carcinomas.

OBJECTIVE: We wanted to identify genes up-regulated in ovarian tumors that might serve as early markers for ovarian cancer. One promising focus is the family of genes that encode secreted proteases, which play essential roles in tumor invasion and metastasis. Kallikrein 10 (KLK10) is a member of the kallikrein family of serine proteases which include 15 proteins, including the prostate-specific antigen (PSA), also known as hK3. We investigated whether KLK10 and its related protein, hK10, might serve as equally accurate markers for ovarian carcinoma. METHODS: Transcriptional profiling was performed using RNA isolated from normal ovarian epithelium, ovarian cancer cell lines, and primary ovarian tumors. Microarray data were confirmed by Northern blot analysis of 66 ovarian tumor samples and 6 ovarian cancer cell lines. In situ hybridization and Western blot analysis confirmed the Northern blot findings. RESULTS: KLK10 was more highly expressed by primary ovarian tumors than by NOE. Thirty-two of 35 primary serous ovarian carcinoma samples (91.4%) expressed higher levels of KLK10 than NOE did. Eleven of 15 nonserous epithelial ovarian carcinoma samples (73.3%) and 8 of 11 primary peritoneal carcinoma samples (72.7%) also expressed KLK10. Overall, 84.8% of all epithelial ovarian and peritoneal carcinoma tumor samples showed elevated expression of KLK10. Similarly, Western blot analysis demonstrated that levels of the KLK10-related protein, designated hK10, are elevated in primary ovarian tissue lysates, but the protein is undetectable in immortalized ovarian epithelium. Finally, in situ hybridization established that KLK10 mRNA is much more highly expressed by tumor tissue than by normal epithelium and stromal tissues. CONCLUSIONS: Our data support recent immunoassay findings of elevated levels of hK10 in the tumor tissue and serum of ovarian cancer patients. Thus, it is likely that KLK10 and other kallikreins will serve as useful diagnostic and prognostic markers in patients with ovarian carcinoma.

Biomarkers, Tumor↗

Benign cystic mesothelioma of the peritoneum: a clinicopathologic study of 17 cases and immunohistochemical analysis of estrogen and progesterone receptor status.

Benign cystic mesothelioma (BCM) is an uncommon lesion of the peritoneum occurring predominantly in women of reproductive age. Although most patients are managed by surgical resection, a reported high incidence of cyst recurrence has led to the use of hormonal therapy in isolated cases in an attempt to control cyst size and relieve local symptoms. To date, the estrogen receptor (ER) and progesterone receptor (PR) status of BCM has not been evaluated. Here we present our experience with 17 cases (13 women, 4 men) of BCM seen over a 19-year period, including an immunohistochemical analysis of ER and PR status in 14 cases. All lesions showed typical morphological features of BCM, and calretinin immunostaining was positive in 14 of 14 cases. Five patients experienced either 1 or 2 tumor recurrences, and no patients died of disease. One case was diffusely positive for ER only, 1 case was focally positive for PR only, and 1 case was focally positive for both ER and PR. Although immunohistochemical detection of female sex hormone receptors in BCM is uncommon, the focal presence of ER and/or PR in some lesions does provide weak biologic support for the use of hormonal manipulation as a therapeutic option. Hum Pathol 34:369-374.

Adolescent↗

Metastatic tumors of the vulva: a clinicopathologic study of 66 cases.

Metastatic tumors involving the vulva are rare, with only a few series and case reports published in the English literature to date. In this study, we present the clinicopathologic features of 66 cases of metastatic tumors of the vulva seen at the University of Texas M. D. Anderson Cancer Center from 1944 to 2001. The patients' age ranged from 18 to 84 years (mean 54.8 years). The most common presentations were vulvar nodules or a mass (39 cases), pain (7 cases), and ulceration (5 cases). In 46.9% of cases, the primary tumor was of gynecologic origin, whereas in 43.9% of cases the primary tumor was of nongynecologic origin. The remainder had unknown primaries. The site most frequently involved by metastasis was the labium majus (44 cases: 18 on the right, 13 on the left, 6 bilateral, and 7 unspecified side). Thirty percent of the patients received chemotherapy as treatment for the metastasis, 27% received radiotherapy, and the rest received some combination of chemotherapy, radiotherapy, and surgery. Of the 60 patients with available follow-up, 52 died of disease within 1-81 months (median 7.5 months) from diagnosis of the metastasis. Metastatic tumors of the vulva are rare; however, the diagnosis of these tumors is facilitated by the knowledge of a preexistent malignancy and the lack of a mucocutaneous intraepithelial lesion.

Adolescent↗

Metastatic melanoma to the vagina: clinicopathologic and immunohistochemical study of three cases and literature review.

We report the clinicopathologic features of three cases of malignant melanoma metastatic to the vagina; only one similar case has been previously reported. The age of the patients ranged from 33 to 70 years; two presented with vaginal bleeding. Two patients had a history of a previous primary malignant melanoma, one a preauricular melanoma treated 7 years earlier and the other a vulvar melanoma treated 2 years earlier. In the third case, a primary malignant melanoma was found on the sole of the right foot after the patient had presented with the vaginal metastases. On gross examination, the vaginal tumors were polypoid; two were on the posterior wall and one was on the anterior wall. All were of epithelioid cell type and were positive with S-100 and microphthalmia-transcription factor. Tyrosinase was positive in two cases, HMB-45 was positive in one case, and MART-1 was focally positive in one case. One patient underwent wide local excision of tumor followed by chemotherapy, one patient had intracavitary radiotherapy, and one had palliative radiotherapy to the brain only. The patients died after a follow-up of 3, 14, and 48 months.

Adult↗

Ovarian steroid cell tumors: an immunohistochemical study including a comparison of calretinin with inhibin.

Ovarian steroid cell tumors, not otherwise specified (SCTs, NOS) are uncommon sex cord-stromal tumors that may be difficult to distinguish from other oxyphilic or clear-cell neoplasms. Immunohistochemical staining for inhibin, although generally useful in the diagnosis of SCTs, NOS, is not positive in every case and not all laboratories have this marker available. Recently, it has been reported that calretinin is expressed by sex cord-stromal tumors. We studied six SCTs, NOS for both calretinin and inhibin expression to evaluate the sensitivity of calretinin in comparison to inhibin. We also tested for CD99, Melan-A (A103), and S-100, other markers reported to be positive in these tumors. HMB-45 and MART-1 (Ab3) completed our panel of markers. All six tumors were positive for both calretinin and inhibin. Calretinin positivity was present in 60% to >90% of tumor cells, whereas inhibin reactivity ranged from <5% to >90% of tumor cells. Membranous staining for CD99 was present in one tumor. S-100-positive cells were seen in two tumors, whereas four tumors were immunoreactive for HMB-45. All six tumors were positive for Melan-A (A103), but in general the staining was less diffuse than with calretinin. All of the tumors were essentially negative for MART-1 (Ab3). The consistent diffuse staining of the tumors in this study for calretinin, in comparison to inhibin and Melan-A (A103), suggests that it is a sensitive marker for SCTs, NOS. MART-1 (Ab3) immunostaining may be useful for cases in which melanoma is considered in the differential diagnosis.

Biomarkers, Tumor↗

Tissue macroarray: a simple and cost-effective method for high-throughput studies.

The tissue microarray technique is a powerful technique that can examine many clinical specimens in a single slide. However, this technique requires a specialized instrument for the construction of tissue microarray block. The authors describe an alternative tissue macroarray technique for the simultaneous analysis of multiple clinical specimens on a single slide. As an example of this method, the authors assembled 12 tumor samples from 12 different paraffin blocks on a glass slide and then immunostained with hMLH1 antibody. This simple method does not need specialized equipment and should be an alternative efficient approach for large-scale clinical specimens.

Antibodies, Monoclonal↗

Calcifications in ovary and endometrium and their neoplasms.

In this study, we investigated the role of hormones in the pathogenesis of calcifications in ovary and in endometrium and their neoplasms of the gynecologic tract and assessed the anatomic location and incidence of these calcifications. The study consists of three parts designed to investigate the pathogenesis, the location, and the incidence of calcifications in ovary and endometrium and their neoplasms. In the first part, 79 female guinea pigs were divided into 10 groups, and different hormones, given weekly for 12 months, were administered to the guinea pigs by group. A control group of 7 guinea pigs received sterile water. Calcifications developed in 5 of 7 guinea pigs treated with prolactin, 10 of 20 treated with human chorionic gonadotropin, 5 of 11 treated with estradiol, 3 of 7 treated with estrone, 1 of 6 treated with growth hormone, and 1 of 10 treated with testosterone; in 20 of the guinea pigs, the calcifications developed in the stroma of the endometrium, and in 5 guinea pigs, they developed in the ovary. The second part of the study consisted of an evaluation of the specific location of calcifications in 43 consecutive human surgical ovaries and endometria. Calcifications were seen only in the stroma in 100% of the ovarian serous adenofibroma specimens; in ovarian serous borderline neoplasms, the stroma contained 70 to 100% of the calcifications, and the epithelium had 0 to 30% of the calcifications. In ovarian serous carcinoma specimens, the calcifications were seen in the stroma in 50 to 60% of the cases, in the epithelium in 40% of the cases, and in areas of necrosis in 10% of the cases. The third part of the study was directed to determine the frequency of calcifications in ovarian lesions. We found that all cases of endosalpingiosis and ovarian low-grade serous carcinoma had calcifications, whereas 80% of the cases of serous borderline tumor had calcifications, and only 50% of the cases of ovarian high-grade serous carcinoma contained calcifications. The results of this study indicate that the majority of the calcifications in the ovary and the endometrium and their neoplasms are present in the stroma. This is most probably secondary to metabolic changes, which could be related to hormones and not caused by degenerative changes in epithelial cells.

Animals↗

Ovarian sex cord-stromal tumors: an immunohistochemical study including a comparison of calretinin and inhibin.

Because ovarian sex cord-stromal tumors (SCST) are morphologically heterogeneous neoplasms that are relatively infrequently encountered, their diagnosis can be difficult. Immunohistochemical staining may be useful for establishing the diagnosis in problematic cases. We studied 53 ovarian SCSTs to characterize their immunohistochemical staining pattern: 17 adult granulosa cell tumors (AGCTs), 4 juvenile granulosa cell tumors (JGCTs), 3 sex cord tumors with annular tubules (SCTATs), 9 Sertoli-Leydig cell tumors (SLCTs), 10 fibromas, 5 fibrothecomas (FTs), and 5 thecomas. In 8 of the 53 cases, the tissue studied was from a metastatic site. The immunopanel included calretinin, inhibin, WT1, cytokeratin cocktail, epithelial membrane antigen (EMA), and cytokeratin 5/6 (CK5/6). The fibromas and FTs were also tested with CD10. The extent of staining was assessed in a semiquantitative fashion and ranked on a scale of 0 through 4+. All of the tumors, except for 1 metastatic SLCT, were positive for calretinin. Forty-five of the cases (85%) stained for inhibin; 1 metastatic AGCT, 3 fibromas, and 4 FTs were negative. WT1 was present in 39 tumors (74%), with expression most prominent in the SLCTs. The cytokeratin cocktail stained 23 of the 53 tumors (43%), whereas just 1 tumor was positive for EMA (1+ in a JGCT). All tumors were negative for CK5/6, and the 15 fibromas and FTs were negative for CD10. We conclude that because cytokeratin is frequently expressed by SCSTs, in particular by granulosa cell tumors, SLCTs, and SCTATs, the inclusion of EMA in a panel may help to exclude epithelial neoplasms. In addition, WT1, present in normal granulosa cells, is expressed by a majority of SCSTs. Finally, these results demonstrate that calretinin is at least as sensitive as inhibin for ovarian SCSTs overall and that it is more sensitive than inhibin for fibromas and FTs.

Biomarkers, Tumor↗

Uterine tumor resembling ovarian sex-cord tumor: report of a case mimicking cervical adenocarcinoma.

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are unusual neoplasms with histologic features that resemble those within ovarian Sertoli and granulosa cell tumors. We report the case of a 24-year-old woman with a UTROSCT presenting as a cervical mass, which on initial evaluation was thought to represent cervical adenocarcinoma. The patient's cervical biopsy specimen contained epithelioid cells arranged in tubules and anastomosing cords, without significant cellular atypia or mitotic activity. Because this morphology elicited a broad differential diagnosis, immunohistochemical studies were performed. The tumor was found to be diffusely positive for cytokeratin cocktail, calretinin, and desmin, focally positive for CK7 and SMA, and negative for EMA, CEA, inhibin, CD10, CK20, chromogranin, and synaptophysin. Ultrastructural examination revealed occasional gland-like lumens with cells joined by desmosomes and a continuous basal lamina. UTROSCTs have features that may cause them to be confused with more common tumors, especially in limited biopsy samples, and should be included in the differential diagnosis when a gland-forming neoplasm with an unusual appearance is identified in a cervical or endometrial biopsy specimen.

Actins↗

Wolffian duct tumors: case reports and review of the literature.

BACKGROUND: Female adnexal tumors of probable wolffian origin are a distinctive epithelial neoplasm arising from the remnants of the mesonephric duct. Although generally considered a tumor of low malignant potential, these tumors can recur. Two cases are reported here. CASES: (1) A 38-year-old G(6)P(6) Latin American woman presented with lower abdominal pain and a pelvic mass. She had a history of a total abdominal hysterectomy and bilateral salpingo-oophorectomy with a paratubal nodule found incidentally 3 years prior. The pathologic findings were consistent with a female adnexal tumor of probable wolffian origin. Imaging studies revealed significant metastatic disease throughout her abdomen and pelvis. The recurrence was confirmed at laparotomy and tumor debulking was performed. Four months later the patient suffered a second recurrence and is currently undergoing treatment with systemic therapy. (2) A 71-year-old Caucasian woman who had undergone exploratory laparotomy and tumor reductive surgery for a female adnexal tumor of probable wolffian duct origin was seen for routine evaluation 1 year after her surgery. Her computed tomography scan revealed possible evidence of recurrence. CONCLUSION: Most female adnexal tumors of wolffian origin behave in a benign fashion. However, there is a potential risk of recurrence. Surgical excision by total abdominal hysterectomy and bilateral salpingo-oophorectomy at the time of diagnosis may be the best recommended mode of therapy. The role of adjuvant radiation therapy or chemotherapy remains questionable.

Adult↗

Micropapillary and cribriform patterns in ovarian serous tumors of low malignant potential: a study of 99 advanced stage cases.

Recently some investigators have proposed abandoning the term ovarian serous tumor of low malignant potential (SLMP) and dividing the tumors in this category into two new groups, micropapillary serous carcinoma and atypical proliferative serous tumor, based on the presence or absence of marked epithelial proliferation with a micropapillary or cribriform pattern (MP/CP). We reviewed 99 cases of advanced stage SLMP (FIGO stages II and III) to determine whether the presence or absence of MP/CP predicts the clinical course, thus justifying the proposed change in terminology. Eighteen cases of MP/CP and 81 cases of typical SLMP were identified. The patients with MP/CP ranged from 23 to 59 years of age at the time of diagnosis (median 35 years), whereas those with typical SLMP were 17 to 67 years old (median 38 years). Bilateral ovarian involvement by SLMP was more frequent in the MP/CP cases, 13 of 18 (72%), as compared with the cases with typical SLMP, 46 of 81 (57%). There was a trend toward a greater frequency of invasive implants in MP/CP cases, 3 of 18 (17%) MP/CP versus 5 of 81 (6%) typical. The mean follow-up period was 125 months for MP/CP patients and 132 months for the typical group. Differences in the frequency of recurrence and the progression-free survival between the groups were found to be significant. Fourteen (78%) of the MP/CP patients experienced either progression or recurrence of disease, whereas 25 (31%) of the typical SLMP patients had a recurrence (p = 0.001). The progression-free survival ranged from 3 to 208 months for MP/CP patients versus 15 to 233 months for typical SLMP patients (p <0.0001). The majority of the recurrences in both groups were low-grade serous carcinoma, 11 of 14 (79%) patients with progression/recurrence in the MP/CP group and 17 of 25 (68%) patients with recurrence in the typical group. The overall survival of the patients in the two groups, however, was not significantly different. Five (28%) MP/CP patients and 12 (15%) patients with typical SLMP died of disease (p = 0.11). All 17 of these patients developed serous carcinoma and died secondary to tumor progression. Four of eight (50%) patients with invasive implants and 13 of 91 (14%) patients with noninvasive implants died of disease. Our findings of more frequent bilateral ovarian involvement, more frequent recurrence with a shorter progression-free interval, and the trend toward a more frequent association with invasive implants support the contention that MP/CP SLMP are a distinct subgroup of serous tumors. However, the overall survival of patients with MP/CP SLMP is similar to that of patients with typical SLMP and justifies the retention of tumors with MP/CP within the LMP category. Additionally, our long-term follow-up of patients with typical SLMP indicates that a number of these tumors do not follow a benign course and supports their continued designation as borderline neoplasms.

Adolescent↗

Vaginal melanoma: a clinicopathologic and immunohistochemical study of 26 cases.

Malignant melanomas of the vagina are rare tumors. In this study we present the clinicopathologic features and immunohistochemical analysis of 26 such cases seen in our institution over a period of 30 years. The patients' age ranged from 38 to 90 years (mean 60 years); three patients were premenopausal. Ethnicity was known in 24 patients: 20 white, 2 hispanic, 1 black, and 1 Asian. The most common presenting symptom was vaginal bleeding, followed by vaginal mass. Grossly, the tumor was polypoid-nodular in the majority of cases. The neoplastic cells were epithelioid in 15 cases and spindled in three cases; eight cases had both cell types. Vascular-lymphatic invasion was seen in six cases and perineural invasion was seen in four cases. S-100 was strongly and diffusely positive in 25 of 26 cases (96%). HMB-45 was strongly positive in 16 (62%), 3 (11%) were focally positive, 1 case showed a rare positive cell, and 6 (23%) were negative. With MART-1, 20 cases (77%) were strongly positive, 1 (4%) showed a rare weakly positive cell, and 5 (19%) were negative. Twenty-one cases (81%) expressed tyrosinase and 20 (77%) expressed microphthalmia transcription factor. Twenty cases were Chung's level IV, 3 were level III, and 2 were level II. The patients were treated as follows: anterior exenteration with or without lymph node dissection and with or without radiotherapy (RT) or chemotherapy (CT) (7 cases), wide local excision with or without lymph node dissection and RT/CT (10 cases), hysterectomy with vaginectomy with or without RT/CT (3 cases), vaginectomy with RT (1 case), RT (1 case), and RT and CT (1 case). One patient had palliative RT for the brain metastasis only. Follow-up was available in 23 patients ranging from 3 to 276 months (median 18 months). Local recurrence after primary treatment was seen in six patients and distant metastases in 11 patients. Fifteen patients died of the disease (3-83 months), 4 have no evidence of disease (5-24 months), and 4 are alive with disease (6-276 months). This study confirms the poor prognosis of patients with vaginal melanoma. S-100 remains the most sensitive marker for these tumors. HMB-45 is negative in 23% cases of vaginal melanoma. Tyrosinase and MART-1 are useful markers when S-100 is negative or only focally positive.

Adult↗

Gross deciduosis peritonei obstructing labor: a case report and review of the literature.

Gross deciduosis peritonei is a rare lesion characterized by the presence of grossly visible peritoneal decidual tissue in pregnant women; we present the clinicopathologic features of one such case. A 24-year-old, G4P1A2, Hispanic female underwent cesarean section at 39 weeks' gestation for dystocia related to pelvic masses. Multiple, light tan peritoneal masses involved the cul-de-sac, both ovaries, pelvic wall, omentum, and the large and small bowel. The intraoperative appearance suggested peritoneal carcinomatosis. A right ovarian mass was excised and biopsies were obtained from other sites. Microscopic examination showed the typical features of decidua in all of the lesions. Two weeks postoperatively, the patient was admitted with nausea and vomiting suggestive of a small bowel obstruction, which resolved after 2 days of medical treatment. After a postpartum visit at 5 weeks, the patient was lost to follow-up.

Adult↗

Peritoneal lesions in guinea pigs treated with hormones.

Foci of peritoneal fibrosis frequently occur with ovarian neoplasms, especially those of epithelial type, usually in association with foci of metastatic tumor or implants. However, in the absence of the latter, the presence of fibrosis cannot be clearly explained. To find an explanation for this phenomenon, we investigated the development of hormone-dependent peritoneal changes in guinea pigs. Of the 59 guinea pigs studied, 49 received one of the following hormones or hormone analogs: estradiol, diethylstilbestrol (DES), testosterone, estrone, Megace, human chorionic gonadotropin, Norethin, clomiphene, luteinizing hormone, dienestrol, hexestrol, and tamoxifen, over a period ranging from 3 to 9 months. Ten guinea pigs received sterile water (control cases). Multiple peritoneal fibrous plaques 1 to 7 mm in greatest dimension were found in 5 of 7 guinea pigs that received estradiol, 6 of 8 treated with DES, and 2 of 2 that received hexestrol and estrone. The largest lesions (fibrous polyps up to 1.2 cm in greatest dimension) were seen in those that received estrone; however, this hormone was poorly tolerated, as two of the animals that received it died after 1 and 2 months, respectively. Because DES was the best-tolerated hormone, we administered it to five additional guinea pigs for 12 months. All five developed fibrous plaques; three of them also developed peritoneal fibroleiomyomas. We conclude that estrogens can induce the development of fibrous plaques in the peritoneum and when they are administered for a long period of time they also induce the development of smooth muscle nodules. This finding is relevant to understanding the pathogenesis of both fibrous lesions associated with ovarian tumors and peritoneal leiomyomatosis.

Animals↗

The association of benign and malignant ovarian adenofibromas with breast cancer and thyroid disorders.

An unexpected association with breast cancer and thyroid disorders was found during a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papillary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibromas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thyroid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast cancer and 16% of each one of these groups had thyroid disorders. This unexpected association found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits.

Adenofibroma↗