A matched study of surgically treated stage IB adenosquamous carcinoma and adenocarcinoma of the uterine cervix

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72055/1/j.1525-1438.1993.03040245.x.pd

HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer

Type II endometrial cancers (uterine serous papillary and clear cell histologies) represent rare but highly aggressive variants of endometrial cancer (EC). HER2 and EGFR may be differentially expressed in type II EC. Here, we evaluate the clinical role of HER2 and EGFR in a large cohort of surgically staged patients with type II (nonendometrioid) EC and compare the findings with those seen in a representative cohort of type I (endometrioid) EC. In this study HER2 gene amplification was studied by fluorescence in situ hybridisation (FISH) and EGFR expression by immunohistochemistry. Tissue microarrays were constructed from 279 patients with EC (145 patients with type I and 134 patients with type II EC). All patients were completely surgically staged and long-term clinical follow up was available for 258 patients. The rate of HER2 gene amplification was significantly higher in type II EC compared with type I EC (17 vs 1%, P<0.001). HER2 gene amplification was detected in 17 and 16% of the cases with uterine serous papillary and clear cell type histology, respectively. In contrast, EGFR expression was significantly lower in type II compared with type I EC (34 vs 46%, P=0.041). EGFR expression but not HER2 gene amplification was significantly associated with poor overall survival in patients with type II EC, (EGFR, median survival 20 vs 33 months, P=0.028; HER2, median survival 18 vs 29 months, P=0.113) and EGFR expression retained prognostic independence when adjusting for histology, stage, grade, and age (EGFR, P=0.0197; HER2, P=0.7855). We conclude that assessment of HER2 gene amplification and/or EGFR expression may help to select type II EC patients who could benefit from therapeutic strategies targeting both HER2 and EGFR

Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27695/1/0000081.pd

Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells

In this study, we explore the therapeutic potential of lapatinib a selective inhibitor of both the EGFR and HER2 tyrosine kinases for the treatment of endometrial cancer. The effect of lapatinib on tumour cell growth and receptor activation was studied in a panel of human endometrial cancer cell lines. Candidate molecular markers predicting sensitivity were assessed by baseline gene expression profiling, ELISA, and western blot analyses. Multiple drug effect/combination index (CI) isobologram analysis was used to study the interactions between chemotherapeutic drugs and lapatinib. Concentration-dependent anti-proliferative effects of lapatinib were seen in all endometrial cancer cell lines tested, but varied significantly between individual cell lines (IC50 range: 0.052–10.9 μmol). HER2 overexpression or increased expression of EGFR was significantly associated with in vitro sensitivity (P=0.024 or 0.011, respectively). Lapatinib exerts growth inhibition in a PTEN-independent manner. Sensitive cell lines also exhibited increased expression of EGFR ligands or HER3. In contrast, lapatinib-resistant cell lines exhibited high androgen receptor (AR) levels or epithelial-to-mesenchymal transition (post-EMT) features. In endometrial cancer cells, at a wide range of clinically achievable drug concentrations, additive and synergistic interactions were observed for lapatinib plus carboplatin, paclitaxel, docetaxel, and doxorubicin. These observations provide a clear biologic rational to test lapatinib as a single agent or in combination with chemotherapy in endometrial cancer with HER2 overexpression. Expression of EGFR, its ligands, HER3, AR, and post-EMT markers warrant further evaluation to help define patients with HER2-nonoverexpressing endometrial cancer most likely to benefit from lapatinib

Lymphatic mapping and sentinel node biopsy in gynecological cancers: a critical review of the literature

Although it does not have a long history of sentinel node evaluation (SLN) in female genital system cancers, there is a growing number of promising study results, despite the presence of some aspects that need to be considered and developed. It has been most commonly used in vulvar and uterine cervivcal cancer in gynecological oncology. According to these studies, almost all of which are prospective, particularly in cases where Technetium-labeled nanocolloid is used, sentinel node detection rate sensitivity and specificity has been reported to be 100%, except for a few cases. In the studies on cervical cancer, sentinel node detection rates have been reported around 80–86%, a little lower than those in vulva cancer, and negative predictive value has been reported about 99%. It is relatively new in endometrial cancer, where its detection rate varies between 50 and 80%. Studies about vulvar melanoma and vaginal cancers are generally case reports. Although it has not been supported with multicenter randomized and controlled studies including larger case series, study results reported by various centers around the world are harmonious and mutually supportive particularly in vulva cancer, and cervix cancer. Even though it does not seem possible to replace the traditional approaches in these two cancers, it is still a serious alternative for the future. We believe that it is important to increase and support the studies that will strengthen the weaknesses of the method, among which there are detection of micrometastases and increasing detection rates, and render it usable in routine clinical practice

Re: Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: Randomized clinical trial

The role of lymphadenectomy in endometrial cancer is a matter of controvers

Lymphadenectomy in endometrial cancer

Not availabl