Biomedical subjects

K C Podratz

Publications and source records attributed to K C Podratz.

At least 19 recordsLinked to original sources

PubMed2006

Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1.

BACKGROUND: Survivin, a novel inhibitor of apoptosis, is one of the most cancer-specific proteins identified to date. In this study we (a) evaluated the association between survivin and HER2, vascular endothelial growth factor (VEGF) and uPA/PAI-1 expression and (b) defined its effect on clinical outcome in a large breast cancer patient cohort. PATIENTS AND METHODS: Survivin expression was measured by ELISA in primary breast cancer tissue extracts from 420 patients with long-term clinical follow-up. RESULTS: Survivin was detected in 378 (90%) of the 420 primary breast cancer cases. Increased survivin levels were significantly associated with high nuclear grade (P < 0.0001), negative hormone receptor status (P = 0.0028), HER2 overexpression (P = 0.0094), VEGF expression (P < 0.0001), high uPA (P = 0.0002) and PAI-1 levels (P = 0.0002). Using the 25th percentile (1.4 ng/mg) as a cut-off point, patients expressing elevated survivin had a significantly worse disease-free survival (DFS: P = 0.0007, RR 1.97) and overall survival (OS: P = 0.0009, RR 2.11) compared with patients expressing lower levels of survivin. In multivariate analysis, this prognostic value of survivin was independent of both traditional and novel clinicopathologic factors for both DFS (P = 0.0076, RR 1.72) and OS (P = 0.0155, RR 1.76). CONCLUSIONS: The independent prognostic relevance of survivin, when combined with previous data from model systems implicating survivin in the inhibition of apoptosis, suggests that survivin may be a suitable target for future therapeutic strategies.

Breast Neoplasms↗

PubMed2002

EGF/ErbB receptor family in ovarian cancer.

In summary, the EGF/ErbB family of receptor tyrosine kinases has been shown to play a key role in normal ovarian follicle development, and cell growth regulation of the ovarian surface epithelium. Disregulation of these normal growth regulatory pathways, including overexpression and/or mutation of EGFR/ErbB receptor family members, as well as elements of their downstream signalling pathways, have been shown to contribute to the etiology and progression of epithelial ovarian cancer. It is, therefore, not surprising that these gene products, and their related soluble receptor isoforms may have clinical utility as tumor and/or serum biomarkers of disease activity. Moreover, since several of these soluble receptor isoforms have potent growth inhibitory activity, and are naturally occurring in the circulation, they are ideal candidates for the development of novel therapeutics for the treatment of ovarian cancer patients.

Binding Sites↗

PubMed2001

Significance of pathologic patterns of pelvic lymph node metastases in endometrial cancer.

OBJECTIVE: The aim of this study was to correlate the pathologic characteristics of pelvic lymph node metastases with survival, recurrence, and patterns of recurrence in endometrial cancer. METHODS: Sixty patients with epithelial endometrial cancer and pelvic node metastasis were managed surgically between 1984 and 1993 at the Mayo Clinic. The mean number of nodes harvested was 16.7 and the mean number of nodes positive was 3.0. Mean follow-up was 45.5 months. The pathologic patterns of lymph node metastases were characterized. RESULTS: Outcome was related to pathologic patterns of pelvic node metastasis. Both diameter of lymph node metastasis (P < 0.01) and capsular integrity (P < or = 0.01) influenced 5-year disease-related survival and 5-year progression-free survival. The percentage of biopsied pelvic lymph nodes harboring metastatic disease and the proportion of the involved lymph nodes occupied by tumor significantly influenced death rates and recurrence rates (P < 0.05). The immune response and the absolute number of positive pelvic nodes did not impact recurrence or survival. The above characteristics of pelvic node metastasis correlated also with patterns of recurrence. Regression analysis indicated that capsular integrity (RR = 2.97; P = 0.005) and proportion of positive pelvic nodes biopsied (RR = 3.84; P = 0.01) were significant predictors of recurrence, whereas diameter of metastasis (RR = 3.68; P = 0.02) and proportion of positive pelvic nodes biopsied (RR = 4.04; P = 0.02) were most predictive of survival. CONCLUSIONS: The pathologic patterns of pelvic node metastasis appear to be significantly related to survival, recurrence, and patterns of recurrence.

Adult↗

PubMed2001

Hematogenous dissemination in corpus cancer.

OBJECTIVE: The aim of this study was to assess the predictors of hematogenous dissemination (HD) in corpus cancer. METHODS: In 612 corpus cancer patients managed surgically, we defined HD as tumor spread to the lung, liver, or other sites via hematogenous routes. RESULTS: We observed 142 instances of tumor spread-71 nonhematogenous and 42 hematogenous to the lung, 9 to the liver, 5 to other sites (adrenals, breast, brain, bone, skin), 3 to both liver and lung, 1 to both lung and bone, and 11 to sites unknown. Stage IV disease, positive adnexae, deep myometrial invasion, primary tumor diameter, tumor involving the whole uterine cavity, positive peritoneal cytology, adjuvant radiotherapy, adjuvant chemotherapy, grade 3 histology, histologic subtype, and lymph-vascular invasion significantly (P < or = 0.01) correlated with HD. However, deep myometrial invasion was the only independent predictor of HD. Only 5% of patients with < or = 50% myometrial invasion had HD compared with 23% with > 50% myometrial invasion. Considering separately recurrence in the lung and in the liver and recurrence in other sites, the only independent predictors of lung recurrence were stage IV disease and myometrial invasion, whereas independent predictors of HD to the liver/other sites were age and histologic grade. Considering only the 60 patients with a known site of HD, 67% with lung recurrence were > 65 years old compared with 17% with HD to the liver/other sites. Furthermore, grade 1-2 disease was observed in 65% of patients with lung recurrence compared with 27% with HD to the liver/other sites. CONCLUSIONS: The presence of deep myometrial invasion was the strongest predictor of HD in corpus cancer, and, together with stage IV disease, it independently predicted lung recurrence. Recurrence in the lung was more frequent in older patients with well or moderately differentiated tumors, whereas HD to the liver/other sites was more frequent in patients < or = 65 years of age harboring grade 3 tumors.

Adult↗

PubMed2001

Routes of lymphatic spread: a study of 112 consecutive patients with endometrial cancer.

OBJECTIVE: The goal of this work was to assess different patterns of lymphatic spread to pelvic and para-aortic lymph nodes (LNs) in endometrial cancer as a function of the location of tumor within the uterus. METHODS: Between 1984 and 1999, 625 patients with endometrial cancer were managed with hysterectomy and node dissection at our institution. The present study includes the 112 (18%) patients who had positive pelvic and/or para-aortic LNs; 41 (37%) of them had cervical involvement. RESULTS: The external iliac was the most commonly involved pelvic LN site both in patients with tumor limited to the corpus and in those with cervical invasion. Isolated pelvic LN metastases to a single site were more frequently observed in external iliac LNs and obturator LNs in patients with tumor confined to the uterine corpus, whereas they occurred more commonly in external iliac and common iliac LNs in patients with cervical involvement. Metastasis to the common iliac LNs was more frequent in patients with disease extension to the cervix. In fact, common iliac LNs were positive in 67% of patients with cervical invasion, compared with only 30% of those with tumor confined to the uterine corpus (P < 0.01). Para-aortic LN invasion was significantly associated with obturator LN status. In fact, para-aortic LNs were positive in 64% of patients with positive obturator LNs compared with 23% of patients with negative obturator LNs (P = 0.01). All patients with positive para-aortic LNs and tumor invading the cervix had positive common iliac LNs. By contrast, when tumor was limited to the corpus, common iliac LNs were involved in only 27% of patients with positive para-aortic LNs. CONCLUSION: External iliac LNs are the most commonly involved LNs in endometrial cancer. Compared with carcinomas limited to the uterine corpus, endometrial cancers invading the cervix spread more readily to the common iliac LNs. Furthermore, these data suggest that para-aortic LN metastases spread via a route shared by the common iliac LNs when tumor involves the cervix but spread predominantly via a route common to the obturator LNs (and/or external iliac LNs) when the primary tumor site is the corpus only.

Adult↗

PubMed2001

Telomerase activity in sex cord-stromal tumors of the ovary.

OBJECTIVE: Telomerase is a ribonucleoprotein that protects chromosomes from degradation and end-to-end fusions by maintaining telomere length. Studies have shown that telomerase is present in 95% of gynecologic malignancies and in 88% of epithelial ovarian carcinomas but undetectable in benign tissue. The aim of this investigation was to determine whether telomerase is present in sex cord-stromal tumors and whether telomerase activity is indicative of patient outcomes. METHODS: Forty-five consecutive sex cord-stromal ovarian tumors were analyzed by using reverse transcription-polymerase chain reaction for expression of human telomerase, human telomerase reverse transcriptase, and telomerase activity. RESULTS: Of the 29 patients with malignant cell types (granulosa cell, Sertoli-Leydig cell, and steroid cell tumors), 21 of the 28 patients (75%) available for follow-up had recurrence, with a mean follow-up of 86 months (95% CI, 36-157 months). The telomerase repeat amplification protocol assay had a sensitivity of 74% and specificity of 94% for malignancy. Patients with telomerase-positive tumors had a mean disease-free interval of 66.5 months; for those with telomerase-negative tumors the interval was 90 months. In addition, patients with telomerase-positive tumors were more likely to be dead from disease or alive with disease than those without telomerase activity, and they showed trends toward requiring a larger number of surgical procedures for the treatment of their disease. However, these trends were not statistically significant. CONCLUSION: Although activation of telomerase is clearly an important step in carcinogenesis, it is unlikely to be helpful in the clinical management of sex cord-stromal tumors of the ovary.

DNA-Binding Proteins↗

PubMed2001

Role of wide/radical hysterectomy and pelvic lymph node dissection in endometrial cancer with cervical involvement.

OBJECTIVE: The goal of this work was to assess retrospectively the role of wide/radical hysterectomy (RH) and pelvic lymph node dissection (LND) in endometrial cancer with cervical involvement. METHODS; From 1984 to 1993, 82 patients with endometrial cancer and cervical involvement were surgically managed at our institution. Of 57 patients with stage II (59%) or III (41%) disease receiving no preoperative therapy, 22 (39%) had simple hysterectomy (SH) and 35 (61%) had RH. Forty-four patients (77%) had pelvic LND, and 38 (67%) had adjuvant radiotherapy (RT). Median follow-up was 70 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 73 and 63%, respectively. Five-year DRS and RFS were 68 and 50%, respectively, in the SH group compared with 76% (P = 0.1) and 71% (P = 0.04) in the RH group. Distant recurrences occurred in 45% of patients with SH and in 23% with RH (P = 0.08). Local recurrence rates did not differ significantly. Considering only stage II tumors, we did not observe any recurrence among patients with negative nodes who had RH, irrespective of the administration of adjuvant RT. By contrast, adjuvant RT improved local control (even if not significantly) in stage II patients who had SH. Five-year DRS of stage III patients was 47%, but it was improved by adjuvant RT in the subgroup of patients who had RH. Independent variables associated with prognosis were stage III disease, deep myometrial invasion, RH, and adjuvant RT. CONCLUSION: RH and adjuvant RT appear to improve prognosis in endometrial cancer with cervical involvement. In particular, radical surgery alone is therapeutic in stage II patients with negative nodes, irrespective of the administration of RT. By contrast, RT can possibly improve local control in stage II patients who previously had SH. Overall, stage III patients have a poor prognosis that can be improved by a combination of radical surgery and adjuvant RT; however, associated therapy directed to extrapelvic sites is probably needed in patients with extrauterine disease.

Adenocarcinoma↗

PubMed2001

Expression of estrogen receptor isoforms alpha and beta messenger RNA in vaginal tissue of premenopausal and postmenopausal women.

OBJECTIVE: To determine the messenger RNA expression patterns of estrogen receptor (ER)alpha and ER beta in human vaginal tissue. STUDY DESIGN: Reverse transcriptase-polymerase chain reaction was performed on tissue samples of 75 patients having anterior colporrhaphy (25 premenopausal, 25 postmenopausal receiving estrogen replacement therapy [ERT], 25 postmenopausal not receiving ERT). Levels of mRNA were normalized and ratios were calculated to assess relative levels of expression. RESULTS: All samples showed expression of the ER alpha isoform. Significant differences existed in ER alpha expression among the 3 cohorts (P =.023). Greater differences (P <.001) existed in ER beta expression. For both isoforms, the premenopausal group had the highest level, and the postmenopausal group receiving ERT had the lowest level. No significant difference in ER beta expression existed between postmenopausal groups. CONCLUSION: Significant differences exist between premenopausal and postmenopausal women in presence and expression of ER alpha and ER beta in vaginal tissue. Expression of ER beta markedly declines in menopause, regardless of ERT use.

Adult↗

PubMed2001

A preliminary study of serum concentrations of soluble epidermal growth factor receptor (sErbB1), gonadotropins, and steroid hormones in healthy men and women.

Soluble ErbB (sErbB) growth factor receptors are being investigated as cancer biomarkers. Gonadotropic and steroid hormones have been shown to modulate the expression of ERBB family members in vivo. Accordingly, the range of sErbB1 values and their relationship to gonadotropic and steroid hormones need to be established in healthy subjects to provide a baseline for future clinical studies. We assayed sera from healthy men and women to determine p110 sErbB1 concentrations by acridinium-linked immunosorbent assay (ALISA). Follicle-stimulating hormone (FSH), estradiol, and testosterone concentrations were measured using the ACS:180 Immunoassay Analyzer. Luteinizing hormone (LH) and progesterone concentrations were quantified using the Access Immunoassay System. Unadjusted for age, p110 sErbB1 concentrations in healthy men and women do not differ significantly. However, sErbB1 concentrations show a strong age-gender interaction, increasing with age in men but decreasing with age in women. Consequently, sErbB1 concentrations are significantly higher in premenopausal women compared with either postmenopausal women or age-matched men and in age-matched men compared with postmenopausal women. Serum sErbB1 concentrations show significant negative associations with both FSH and LH concentrations in healthy women and a significant positive association with FSH concentrations in healthy men. Univariate linear regression models show that these respective gonadotropic hormones and age are independent predictors of sErbB1 concentrations in men and women. Multivariate models show that when age and FSH and LH concentrations are mutually adjusted for each other, they account for 22% of the variability observed in sErbB1 concentrations in healthy women. These data support the hypothesis that gonadotropic and steroid hormones may modulate ERBB1 expression in vivo and suggest that age- and gonadotropin-adjusted sErbB1 concentrations may be of clinical utility. Furthermore, these data demonstrate that gender, age, menstrual cycle phase, menopausal status, and exogenous hormone use must be considered when using serum p110 sErbB1 concentrations as cancer biomarkers.

Adult↗

PubMed2000

Squamous cell carcinoma of the vulva stage IA: long-term results.

OBJECTIVE: The aim of this study was to evaluate the risk of metastases to lymph nodes and long-term results of radical and modified radical surgery in patients with a T1 squamous cell carcinoma of the vulva and </=1 mm of invasion. METHODS: A retrospective review of 40 patients with T1 squamous cell carcinoma of the vulva and </=1 mm of invasion was performed. The clinical, pathologic, surgical, and follow-up data were abstracted from the patients' records. All slides were reviewed by two pathologists according to previously established guidelines. The overall mean follow-up was 7.6 years. RESULTS: Vulvar recurrence developed in 2 patients (5-year rate, 5.9%). There were no groin recurrences among 10 patients undergoing groin lymphadenectomy. One of the 30 patients (10-year rate, 6.7%) without groin dissection developed groin metastases at 7.5 years, subsequent to an invasive vulvar recurrence. The 5- and 10-year cause-specific survivals were 100 and 94.7%, respectively. CONCLUSIONS: T1 squamous cell carcinoma of the vulva with </=1 mm of invasion was associated with a low risk of vulvar recurrence and no groin node metastases. A low risk of subsequent groin node metastasis exists in patients developing an invasive vulvar recurrence. Long-term follow-up of these patients is recommended. Lesser forms of vulvar excision, such as wide local excision, were equally effective as radical vulvectomy for the prevention of vulvar recurrences. Patients treated by radical vulvar surgery experienced increased postoperative complications compared with patients treated by less radical surgery.

Adult↗

PubMed2000

Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer.

OBJECTIVE: The aim of this study was to assess the potential therapeutic role of para-aortic lymphadenectomy (PAL) in high-risk patients with endometrial cancer. METHODS: We studied two groups of patients with endometrial cancer who underwent operation at Mayo Clinic (Rochester, MN) during the interval 1984 to 1993: (1) 137 patients at high risk for para-aortic lymph node involvement (myometrial invasion >50%, palpable positive pelvic nodes, or positive adnexae), excluding stage IV disease, and (2) 51 patients with positive nodes (pelvic or para-aortic), excluding stage IV disease. By our definition, PAL required removal of five or more para-aortic nodes. RESULTS: In both groups, no significant difference existed between patients who had PAL (PAL+) and those who did not (PAL-) in regard to clinical or pathologic variables, percentage irradiated, or surgical or radiation complications. Among the 137 high-risk patients, the 5-year progression-free survival was 62% and the 5-year overall survival was 71% for the PAL- group compared with 77 and 85%, respectively, for the PAL+ group (P = 0.12 and 0.06, respectively). For the 51 patients with positive nodes, the 5-year progression-free survival and 5-year overall survival for the PAL- group were 36 and 42% compared with 76 and 77% for the PAL+ group (P = 0.02 and 0.05, respectively). Lymph node recurrences were detected in 37% of the PAL- patients but in none of the PAL+ patients (P = 0.01). Multivariate analysis suggested that submission to PAL was a cogent predictor of progression-free survival (odds ratio = 0.25; P = 0.01) and overall survival (odds ratio = 0.23; P = 0.006). CONCLUSIONS: These results suggest a potential therapeutic role for formal PAL in endometrial cancer.

Aged↗

PubMed2000

Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma.

OBJECTIVE: Our objective was to determine whether cytokinetic and molecular analyses of curettage specimens can provide a mechanism for triage of patients with endometrial cancer before initiating definitive surgical treatment. METHODS: Pretreatment analysis consisted of flow cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohistochemical determination of expression of proliferating cell nuclear antigen, HER-2/neu, and p53 in curettage specimens from 134 patients with endometrial carcinoma who subsequently had surgical staging and definitive surgical treatment. Fisher's exact test or chi(2) was used to examine the association between pretreatment variables and traditional surgical-pathologic indices. The log-rank test was used for univariate survival analysis. Cox proportional hazards identified the most important molecular factors. RESULTS: Nondiploid status, SPF >/=9%, and PI >/=14% were associated with the traditional posttreatment prognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF >/=9%, PI >/=14%, and p53 overexpression and decreased progression-free survival (PFS) and disease-related survival (DRS). Stepwise Cox regression analysis identified p53 overexpression and SPF >/=9% as the most significant pretreatment molecular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that when both factors are present the risk for recurrence was higher (RR = 7.07; 95% confidence interval [CI], 3.06-16.38; P < 0.01) and death due to disease was higher (RR = 9.93; 95% CI, 3.92-25.19; P < 0.01) than when no factors are present. In the group with both factors, 5-year PFS and DRS estimates were 41 and 44%, respectively, compared with 86 and 86% and 90 and 92% for the "none" and "one" groups, respectively. CONCLUSION: When observed simultaneously, increased SPF and p53 overexpression defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens could provide a mechanism of triage that could be applied before definitive surgical treatment.

Adult↗

PubMed2000

Assessment of inhibin and p53 in granulosa cell tumors of the ovary.

OBJECTIVE: The goal of this work was to determine the cellular content of inhibin and p53 in granulosa cell tumors (GCTs). METHODS: Clinical records of 47 patients (mean age, 54 years; range, 20-85 years) presenting with GCT surgically managed at our institution were abstracted. International Federation of Gynecology stage I was assigned in 39 patients, stage II in 2, and stage III in 6. Concomitant endometrial carcinoma was identified in 6 patients. Mean follow-up was 13.6 years (range, 1 day to 37.6 years). Sections from paraffin-embedded tissue blocks were analyzed immunohistochemically for expression of tissue inhibin and p53 levels. Inhibin expression was graded by intensity and reactivity, and p53, by its presence or absence. RESULTS: The tumors of 27 patients (57%) stained strongly for inhibin intensity and showed >60% reactivity. Decreased intensity and reactivity of inhibin expression were associated with advanced-stage disease (P = 0.05 and P < 0.01, respectively, by Fisher exact test). Expression of p53 was detected in tumors from 27 patients (57%), and immunoreactivity was associated with compromised progression-free survival (P = 0.016, log-rank test). However, the association between p53 immunoreactivity and disease stage was not significant. Absence of p53 expression was significantly associated with concurrent endometrial carcinoma (P = 0.022), suggesting more molecularly intact tumors that retain functional activity. CONCLUSIONS: Although the majority of GCTs show strong expression of inhibin with regard to intensity and reactivity, weak expression is associated with advanced disease but not with decreased progression-free survival. By contrast, expression of p53 is not significantly associated with stage, but increased expression is associated with decreased disease-free survival. Absence of p53 expression appears to be associated with concurrent endometrial carcinoma.

Adult↗

PubMed2000

Surgical management of desmoid tumors of the female pelvis.

BACKGROUND: Desmoid tumors are neoplasms characterized by proliferation of fibroblasts without cytologic features of malignancy. Although desmoid tumors are not uncommon, pelvic desmoid tumors are rare and therapeutically challenging. We describe the surgical management of seven patients with histologically confirmed desmoid tumors arising in the pelvis. STUDY DESIGN: All patients, six with primary and one with recurrent desmoid tumors of the female pelvis, were treated at Mayo Clinic Rochester between 1976 and 1997. The mean age of one African-American and six Caucasian patients was 29.8 years (range 17 to 59 years). No history of previous relevant pelvic trauma was identified; six patients experienced pelvic or leg pain (or both). All patients presented with isolated masses; five of seven were located left of the midline, generally involving the obturator internis or levator muscles (or both). The surgical approach was transabdominal, with a vaginal component in one patient. In addition to this retrospective review of these seven patients, literature addressing the management of desmoid tumors of the female pelvis is reviewed. RESULTS: Extirpative surgery necessitated resection of musculoskeletal, vascular, or adjacent soft tissue structures. Mean tumor diameter was 13.9cm (range 5 to 27 cm). Although the median recorded blood loss was 1,425mL, one patient who refused blood products died secondary to surgical hemorrhage. The median followup for the remaining evaluable patients was 57 months (range 13 to 249 months). Recurrent disease developed in 3 of 6 patients at 3, 11, and 13 months after surgical resection and was successfully managed with subsequent reoperations, with or without adjuvant radiotherapy. CONCLUSIONS: Although recent reports demonstrate selective regression of desmoid tumors with antiestrogen therapy, management of symptomatic pelvic desmoid tumors in young women may necessitate an operation. In our series, all primary and recurrent tumors were managed with resection of involved bone and other adjacent soft tissues. The role of adjunctive radiotherapy or hormonal therapy remains to be defined.

Adolescent↗

PubMed2000

Pretreatment assessment of prognostic indicators in endometrial cancer.

OBJECTIVE: The object of this study was to assess the association of histologic, cytokinetic, and molecular variables in preoperative endometrial samples with extrauterine disease, recurrence, and survival among patients with endometrial cancer. STUDY DESIGN: In a case-cohort study of 125 women, ploidy, S-phase fraction, proliferative index, deoxyribonucleic acid index, proliferating cell nuclear antigen, MIB-1 proliferation marker, p53 tumor suppressor gene, and cytoplasmic HER-2/neu oncogene and bcl-2 expressions were quantitated. RESULTS: A model with only one independent term predicted progression-free survival; that variable was p53 (P <. 0001; relative risk, 5.60). A model with two independent terms predicted disease-related survival; these variables were p53 (P =. 0002; relative risk, 7.39) and MIB-1 (P =.03; relative risk, 3.27). Among patients with tumors with both p53 and MIB-1 expression exceeding 33%, a total of 32% had died of disease by 2 years. A model for predicting extrauterine disease selected two independent variables: p53 (odds ratio, 3.20; P =.01) and ploidy (odds ratio, 2. 16; P =.04). An advanced surgical stage was encountered in 26% to 35% of cases in which either the p53 expression exceeded 33% or the deoxyribonucleic acid content was nondiploid and in 53% of cases in which both variables were unfavorable. CONCLUSIONS: Preoperative evaluation of quantifiable cytokinetic and molecular variables can assist in identifying tumor types that are predisposed toward a more aggressive clinical course.

Adult↗

PubMed2000

Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary?

OBJECTIVE: The objective of this study was to find readily ascertainable intraoperative pathologic indicators that would discriminate a subgroup of early corpus cancers that would not require lymphadenectomy or adjuvant radiotherapy. STUDY DESIGN: Between 1984 and 1993, a total of 328 patients with endometrioid corpus cancer, grade 1 or 2 tumor, myometrial invasion < or =50%, and no intraoperative evidence of macroscopic extrauterine spread were treated surgically. Pelvic lymphadenectomy was performed in 187 cases (57%), and nodes were positive in nine cases (5%). Adjuvant radiotherapy was administered to 65 patients (20%). Median follow-up was 88 months. RESULTS: The 5-year overall cancer-related and recurrence-free survivals were 97% and 96%, respectively. Primary tumor diameter and lymphatic or vascular invasion significantly affected longevity. No patient with tumor diameter < or =2 cm had positive lymph nodes or died of disease. CONCLUSION: Patients who have International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid corpus cancer with greatest surface dimension < or =2 cm, myometrial invasion < or =50%, and no intraoperative evidence of macroscopic disease can be treated optimally with hysterectomy only.

Adult↗

PubMed1999

Preoperative serum level of inhibin A is an independent prognostic factor for the survival of postmenopausal women with epithelial ovarian carcinoma.

BACKGROUND: The aim of this study was to determine the prognostic significance of preoperative serum inhibin and activin levels in postmenopausal women with epithelial ovarian carcinoma (EOC) by correlating serum levels with disease parameters, including tumor stage and grade and patient age. METHODS: Serum levels of inhibin A, inhibin B, pro-alpha C, activin A, and activin B were quantitated with sensitive and specific two-site enzyme-linked immunosorbent assays (ELISAs) in samples collected from 44 postmenopausal women diagnosed with EOC. Serum was obtained within 14 days prior to primary tumor reductive surgery and stored at -55 degrees C. All patients underwent definitive surgical staging and cytoreduction at Mayo Clinic and were followed for at least 5 years or until death. Postoperative adjuvant therapy was selected based on stage of disease. Demographics included 5 Stage I, 2 Stage II, 33 Stage III, and 4 Stage IV tumors, and the predominant histology was serous subtype and poorly differentiated grade. RESULTS: Inhibin A was detected in 98% of the serum samples (range, 0-12.18 pg/mL). Univariate analysis was used to demonstrate an association between patients with serum inhibin A levels exceeding the median (1.21 pg/mL) and compromised disease free (P = 0.025) and overall (P = 0.006) survival. While the 5 year disease free survival (DFS) for the entire population was 32%, the corresponding DFS rates for patients with inhibin A levels above and below the median were 10% and 43%, respectively. Similarly, the 5-year overall survival (OS) for the entire population was 35%, compared with 16% for patients above and 47% for patients below the median inhibin A level. Stepwise regression analysis that incorporated age, stage, grade, and inhibin A levels identified serum inhibin A levels above the median to be the most cogent predictor of DFS and OS. CONCLUSIONS: Preoperative serum inhibin A levels provided valuable prognostic information independent of age, stage, and grade in a postmenopausal cohort given standardized treatment for EOC.

Aged↗

PubMed1999

Loss of markers linked to BRCA1 precedes loss at important cell cycle regulatory genes in epithelial ovarian cancer.

Advanced-stage epithelial ovarian cancers (EOC) from 114 patients were assessed for loss of heterozygosity (LOH or allelic imbalance) at several tumor suppressor gene loci as an initial step in identifying gene alterations important to the development of these tumors. The highest frequency of loss, 84% (86 of 102 cases), was observed for markers mapping near or within BRCA1; other significant frequencies of LOH were observed for loci mapping near or within CDKN2A/CDKN2B (56%), BRCA2 (61%), RB1 (67%), or TP53 (73%). No instance of TP53 LOH was observed without simultaneous allelic imbalance at the BRCA1 region (P = 0.0005). LOH of CDKN2 without loss near the BRCA1 region was seen in only 2 of 75 cases (P < 0.0001), and RB1 LOH without BRCA1 loss occurred in only 1 of 35 tumors (P = 0.0703). These data suggest that LOH of BRCA1, or a closely linked locus, precedes the loss of CDKN2, TP53, and RB1, and imply that inactivation of a tumor suppressor gene in this region is an important early step in the development of these tumors.

Adult↗