Feasibility of endometrial sampling by vaginal tampons in women with Lynch syndrome.

Background: Endometrial sampling for the surveillance of women with Lynch syndrome is an invasive and painful procedure. The aim of this study was to evaluate the feasibility of a less invasive procedure of collecting vital cells by vaginal tampons.

Methods: This was a prospective feasibility study of women scheduled to undergo annual gynecological surveillance, including endometrial sampling.

Margin status revisited in vulvar squamous cell carcinoma.

Objective: To determine the incidence of local recurrence of vulvar squamous cell carcinoma in relation to tumor- and/or precursor lesion free pathologic margins.

Methods: Consecutive patients with primary vulvar squamous cell carcinoma surgically treated in two Dutch expert centers between 2000 and 2010 were included. All pathology slides were independently reviewed by two expert gynecopathologists, and local recurrence was defined as any recurrent disease located on the vulva.

Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: A systematic review.

Background: In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be helpful to select high risk patients and/or to develop strategies to prevent local recurrences.

Objective: This systematic review aims to evaluate the current knowledge on the incidence of local recurrences in vulvar carcinoma related to clinicopathologic and cell biologic variables.

Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre- versus post-operative risk stratification.

Background: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival.

Methods: Patients diagnosed with EC within the first 6 months of the years 2005-2014 were selected from the Netherlands Cancer Registry (N = 7875).

CD103 defines intraepithelial CD8+ PD1+ tumour-infiltrating lymphocytes of prognostic significance in endometrial adenocarcinoma.

Introduction: Intraepithelial CD8+ tumour-infiltrating T-lymphocytes (TIL) are associated with a prolonged survival in endometrial cancer (EC). By contrast, stromal infiltration of CD8+ TIL does not confer prognostic benefit. A single marker to discriminate these populations would therefore be of interest for rapid assessment of the tumour immune contexture, ex vivo analysis of intraepithelial and stromal T-cells on a functional level and/or adoptive T-cell transfer.

Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer.

Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment of surgical resection and (neo-)adjuvant chemotherapy. To address this outstanding issue, we compared TIL infiltration in a unique cohort of patients with advanced-stage HGSC primarily treated with either surgery or neoadjuvant chemotherapy.

Sentinel node biopsy in vulvar cancer: Implications for staging.

In 2008, the first Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V) showed that omission of inguinofemoral lymphadenectomy is safe in patients with early-stage vulvar cancer and a negative sentinel node and it simultaneously decreases treatment-related morbidity. An important part of the sentinel node procedure is pathologic ultrastaging of the removed sentinel nodes. Subsequently, since the introduction of this procedure in the standard care of patients with early-stage vulvar cancer, more and smaller inguinofemoral lymph node metastases have been diagnosed.

Assessment of estrogen receptor expression in epithelial ovarian cancer patients using 16α-18F-fluoro-17β-estradiol PET/CT.

Unlabelled: The estrogen receptor α (ERα) is expressed in approximately 70% of ovarian cancer tumors. PET of tumor ERα expression with the tracer 16α-(18)F-fluoro-17β-estradiol ((18)F-FES) may be valuable to select ovarian cancer patients for endocrine therapy. The aim of this study was to evaluate the feasibility of (18)F-FES PET to determine tumor ERα expression noninvasively in epithelial ovarian cancer patients.

Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: pooled results from three countries.

Introduction: Tamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer.

Methods: We pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status.

Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma.

Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma.

Gene promoter methylation patterns throughout the process of cervical carcinogenesis.

Objectives: To determine methylation status of nine genes, previously described to be frequently methylated in cervical cancer, in squamous intraepithelial lesions (SIL).

Methods: QMSP was performed in normal cervix, low-grade (L)SIL, high-grade (H)SIL, adenocarcinomas and squamous cell cervical cancers, and in corresponding cervical scrapings.

Results: Only CCNA1 was never methylated in normal cervices and rarely in LSILs.

Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group.

Purpose: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.

Value of RT-PCR analysis of sentinel nodes in determining the pathological nodal status in colon cancer.

Background: Pathological examination of sentinel lymph nodes (SLNs) and non-SLNs in colon cancer is frequently not performed to the same extent. We examined whether non-SLNs were truly negative in tumors with tumor-negative SLNs using reverse transcriptase-polymerase chain reaction (RT-PCR).

Patients And Methods: RT-PCR with carcinoembryonic antigen (CEA) was performed in hematoxylin-eosin (H&E) and immunohistochemical (IHC) tumor-negative SLNs.

In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft.

Unlabelled: Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for noninvasive in vivo VEGF visualization and quantification with the single gamma-emitting isotope 111In and the PET isotope 89Zr.

Determination of TP53 mutation is more relevant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage III colon cancer patients.

Purpose: Microsatellite instability (MSI), TP53 mutation, and KRAS mutation status have been reported as prognostic factors in colon cancer. Most studies, however, have included heterogeneous groups of patients with respect to cancer stage. We determined the prognostic relevance of high-frequency MSI (MSI-H), TP53 mutations, and KRAS mutations in a well-defined group of patients with stage III colon cancer (N = 391), randomly assigned for adjuvant treatment with fluorouracil-based chemotherapy.

Expression of tumour necrosis factor-related apoptosis-inducing ligand death receptors in sporadic and hereditary colorectal tumours: potential targets for apoptosis induction.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and antibodies against TRAIL receptors death receptor 4 (DR4) and death receptor 5 (DR5) are under investigation for cancer therapy. To study the potential application of these agents, the expression of DR4 and DR5 were studied immunohistochemically in colorectal adenomas and carcinomas from patients with sporadic disease (n=74 and 56, respectively), familial adenomatous polyposis (FAP, n=41 and 4, respectively) and hereditary non-polyposis colorectal cancer (HNPCC, n=50 and 21, respectively). BAX, which is frequently mutated in tumours with high-frequency microsatellite instability (MSI-H) may play a role in sensitivity to TRAIL.

Prognostic value of nodal micrometastases in patients with cancer of the gastro-oesophageal junction.

Aims: Aim of this study was to examine the presence and the prognostic impact of immunohistochemically identified nodal micrometastases in patients with gastro-oesophageal junction (GEJ) carcinomas.

Methods: Between January 1988 and December 2000, 148 patients underwent a radical (R0) resection with a two-field lymphadenectomy for a GEJ carcinoma. Specimens of 60 patients in whom conventional haematoxylin and eosin (H & E) examination did not demonstrate lymph-node metastases (pN0) were available for immunohistochemical (IHC) analysis using antibodies AE1/AE3 directed against cytokeratins.

An in vitro model for purging of tumour cells from ovarian tissue.

Background: Cryopreservation and autografting of ovarian tissue may preserve fertility after cancer treatment, but could be hampered by tumour cell contamination. Epithelial tumour cell lysis can be obtained with cytotoxic T cell retargeting through the bispecific antibody BIS-1, with combined affinity for the T-cell receptor and epithelial glycoprotein-2 (EGP-2). Our aim was to study the concept of tumour cell purging in the setting of a suspension of ovarian tissue.

Inclusion of malignant fibrous histiocytoma in the tumour spectrum associated with hereditary non-polyposis colorectal cancer.

Sarcomas, including the malignant fibrous histiocytomas (MFHs), are not known to be part of the tumour spectrum of hereditary non-polyposis colorectal cancer (HNPCC) as epidemiologically established. Therefore, occurrence of MFH in an HNPCC family may very well be coincidental. HNPCC is associated with germline mutations in DNA mismatch repair genes, including the MSH2 gene.

Structural alterations of transforming growth factor-beta receptor genes in human cervical carcinoma.

The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-beta (TGFbeta)-mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGFbeta resistance, we screened the 7 exons of the type II (TbetaR-II) TGFbeta receptor and the 9 exons of the type I (TbetaR-I) TGFbeta receptor genes for mutations in 16 paraffin-embedded primary invasive cervical carcinoma specimens. In one of these carcinomas, we found a novel G-->T transversion in exon 3 of TbetaR-II that introduces a premature stop codon (E142Stop) and presumably results in the synthesis of a truncated soluble exoreceptor.