Josep M. Martinez-Palones

The clinicopathological significance of K-RAS point mutation and gene amplification in endometrial cancer

The aim of this study was to examine the prevalence and clinicopathological significance of K-RAS oncogene activation in endometrial carcinoma and atypical hyperplasia. We analysed K-RAS point mutation and gene amplification in 55 endometrial carcinomas using polymerase chain reaction associated with restriction fragment length polymorphism and genomic differential polymerase chain reaction. Point mutations at codon 12 of K-RAS oncogene were identified in 8 of 55 (14.5%) tumour specimens. In addition, we were unable to detect any K-RAS gene amplification in any of the endometrial carcinomas studied. No correlation was found between K-RAS gene mutation and age at onset, histological subtype, grade of differentiation, clinical stage or current patient status. We conclude that K-RAS mutation is a relatively common event in endometrial carcinomas, but with no clear prognostic value.

Usefulness of sentinel lymph node detection in early stages of cervical cancer

PurposeSentinel lymph node (SLN) mapping in combination with surgical biopsy is an emerging technique for use in the early stages of cervical cancer. The purpose of this study was to evaluate the technique in a series of 40 consecutive women with early stage cervical cancer.MethodsForty patients with early stage cervical cancer [FIGO stage IA2 (2), IB1 (34), IB2 (1) or IIA (3)] were referred for radical hysterectomy with pelvic lymphadenectomy. Patients were submitted to preoperative lymphoscintigraphy (four 99mTc-nanocolloid injections around the tumour) and intraoperative SLN detection. Hand-held or laparoscopic gamma probes were used to locate SLNs during surgery.ResultsThe mean number of SLNs was 2.5 per patient (interiliac 49%, external iliac 19%). Of the total of 99 SLNs, six, in four women, showed metastases (all 68 non-SLNs removed were negative). In the other 36 patients, all the removed lymph nodes (sentinel and non-sentinel) were negative (0% false negative rate). During the follow-up (median 25 months), only two patients presented distant metastases: one died 6 months after surgery (two of three SLNs positive, both hot and blue), while the second patient is alive 4 years after surgery (lung metastasis, no isotope drainage, negative blue SLN). The survival rate was 95% and disease-free survival, 97%.ConclusionSLN surgical biopsy based on lymphoscintigraphy and blue dye is a feasible and useful technique to avoid lymph node dissection in the early stages of cervical cancer. It has a high negative predictive value, can be incorporated into clinical routine (laparoscopy or open surgery) and is close to achieving validation in this setting.

Sentinel lymph node identification in a primary ductal carcinoma arising in the vulva

Primary or metastasic breast-like carcinoma of the vulva is a rare event. Because of the similarity with breast ductal carcinoma, we think that the same principles used for treatment of orthotopic breast cancer can be applied, as well as the use of sentinel lymph node technique, which is widely accepted in the management of early-stage breast cancer. We report a 49-old-year postmenopausal woman who was referred to our institution after small biopsy of a 3.5- × 3-cm right vulvar tumor. Histopathologically, infiltration of the vulvar dermis by a ductal carcinoma of mammary gland type was reported. At operation, the sentinel node technique revealed two sentinel nodes in the right inguinal area. Although these nodes proved negative for malignancy, the patient underwent wide local excision of tumor and complete ipsilateral inguinofemoral lymphadenectomy. The remaining excised nodes were negative. Surgical specimen proved estrogen- and progesterone-positive receptors, the reason for which the patient received tamoxifen adjuvant therapy. This report represents the first case in the world literature of primary breast carcinoma arising in the vulva in which sentinel lymph node identification has been possible. Because of the rarity of this condition, the pathologic similarity of this tumor along with currently accepted guidelines for the management of breast cancer supports the possibility of local excision and sentinel lymph node identification as a possible alternative to inguinofemoral lymphadenectomy

Endometrial carcinoma in tamoxifen-treated breast cancer patient : clinicopathological, immunohistochemical, and genetic analysis

Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in endometrial carcinomas associated with tamoxifen use. In the present case, the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB2/neu, cyclin D1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene. The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in DNA methylation.