Occult endometrial cancer and decision making for prophylactic hysterectomy in hereditary nonpolyposis colorectal cancer patients
Introduction
Hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal-dominantly inherited disorder, is the most frequent hereditary predisposition to colorectal cancer (CRC) and accounts for about 2–4% of the total CRC incidence. It is clinically defined by the Amsterdam criteria [1], [2] and associated with highly penetrant germline mutations in mismatch repair (MMR) genes. Disease causing mutations have been identified in four of these genes to date, namely MLH1, MSH2, MSH6 and PMS2 [3], [4], [5], [6], [7], [8], [9], [10], [11]. There is a high lifetime risk for CRC of 75–92% in MMR genes mutation carriers, including a high rate of synchronous and metachronous CRC [12], [13], [14], [15], [16], [17], [18], [19]. In addition, a remarkably increased risk for extracolonic carcinomas (endometrial, gastric, ovarian, small bowel, renal pelvis or ureter carcinomas) has been reported [14], [15], [16], [20], [21], [22]. Endometrial cancer (EC) is the most frequent extracolonic and gynecologic cancer and its cumulative lifetime risk has been estimated up to 61% [14], [15], [16], [20], [22], [23]. The highest incidence for HNPCC-related EC is between ages 40 and 60, which is significantly earlier than in the general population [20], [23]. The cumulative risk for ovarian cancer is estimated up to 12% [16], [24], [25], [26]. Strict surveillance (clinical examination, colonoscopy, urinary cytological examination and gynecological examination including transvaginal sonography and CA-125 measurement) for HNPCC patients, mutation carriers and persons at risk has been recommended [27], [28], [29], [30], [31]. Although a reduced CRC risk due to surveillance programs has been shown [29], [30], there are only few data available concerning the efficiency and clinical benefit of gynecological surveillance, and solely in few cases the detection of premalignant lesions has been reported [24], [32]. Therefore, the question arises whether prophylactic hysterectomy could be an option in these women.
Hereby, we present a combined clinical and molecular approach based on a retrospective analysis in regard to the decision making as to whether or not to perform a prophylactic hysterectomy with oophorectomy in a subset of HNPCC patients and discuss advantages, disadvantages and indications for this procedure.
Section snippets
Patients and methods
147 female patients meeting at least one criterion of the Bethesda guidelines [33] between 1995 and 2003 were retrospectively analyzed. After they had been given informed written consent, molecular diagnosis, including microsatellite analysis, immunohistochemistry and sequencing of the MMR genes MLH1, MSH2 and MSH6 using peripherial blood and tumor samples was performed. Microsatellite analysis was performed on paired samples of lymphocyte DNA and paraffin-embedded or fresh-frozen tumor tissue
History of EC and molecular data
We have counseled 147 female index patients meeting at least one criterion of the Bethesda guidelines at our out-patient department for hereditary cancer. Twenty-six of them fulfilled the Amsterdam criteria. Molecular diagnostics were initiated, and the disease causing germline mutation in one of the MMR genes could be identified in 31 patients meeting the criteria of the Bethesda guidelines and in 15 patients fulfilling the Amsterdam criteria, respectively (data not shown) [35], [36], [38],
Discussion
Prophylactic procedures before the onset of cancer are well-accepted in other hereditary tumor syndromes such as familial adenomatous polyposis or multiple endocrine neoplasia type II [43], [44]. In these syndromes, the indication for a prophylactic procedure is based on the high penetrance of the causative germline mutation, on a clear genotype–phenotype correlation, on the young age at disease onset and on a poor prognosis of the associated carcinomas. In HNPCC, there is an incomplete
Acknowledgments
We thank Monika Reichmann and Alex Schiewart for excellent technical assistance. This work was supported by the Deutsche Krebshilfe grant “Familiärer Dickdarmkrebs” (70-3032-Scha-4).
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Case report: Muir-Torre syndrome diagnosed from a sebaceoma mimicking an ulcerated breast cancer
2016, Journal de Gynecologie Obstetrique et Biologie de la ReproductionProphylactic Gynecologic Specimens from Hereditary Cancer Carriers
2016, Surgical Pathology ClinicsCitation Excerpt :Chung and colleagues64 identified a mixed clear cell and endometrioid carcinoma of endometrium in a 48-year-old MSH2 carrier. Table 1 summarizes the cancer findings in prophylactic gynecologic specimens from LS patients, including histologic subtypes, gene affected, and patient age.61–67 Currently, it is recommended that women identified as being at genetic risk for LS-associated endometrial and ovarian cancer undergo annual gynecologic examination, pelvic ultrasound, and endometrial biopsy beginning between ages 30 and 35 years.
Prevalence of occult gynecologic malignancy at the time of risk reducing and nonprophylactic surgery in patients with Lynch syndrome
2014, Gynecologic OncologyCitation Excerpt :However, determining the prevalence of occult cancer was not a primary outcome of these studies. Pistorius et al. noted occult endometrial cancer in 2 of 4 patients undergoing risk-reducing surgery for LS [24]. Schmeler et al. noted occult endometrial cancer in 5% of 61 patients undergoing risk-reducing surgery [15].
The additional value of endometrial sampling in the early detection of endometrial cancer in women with Lynch syndrome
2013, Gynecologic OncologyCitation Excerpt :In our study some women reported pain during endometrial sampling as a reason to opt for prophylactic surgery. Prophylactic hysterectomy and bilateral salpingo-oophorectomy can also be offered to women diagnosed with colon cancer during the same surgery [21–23]. In conclusion, annual endometrial screening seems effective in the detection of premalignancies and early endometrial cancer in women with LS in this study.
Lynch or Not Lynch? Is that Always a Question?
2012, Advances in Cancer ResearchCitation Excerpt :Moreover, such analyses are not only useful for detecting LS patients but are also of broader interest in the case of sporadic MSI. Indeed, it is known that MSI tumors have a more favorable outcome than MSS tumors (Popat et al., 2005). Moreover, patients with MSI tumors may not benefit as much from commonly used fluorouracil-based adjuvant chemotherapy as patients with MSS tumors (Ribic et al., 2003).