The special AT-rich sequence-binding protein 2 (SATB2), a nuclear matrix-associated transcription factor and epigenetic regulator, was identified as a tissue type-specific protein when screening protein expression patterns in human normal and cancer tissues using an antibody-based proteomics approach. In this respect, the SATB2 protein shows a selective pattern of expression and, within cells of epithelial lineages, SATB2 expression is restricted to glandular cells lining the lower gastrointestinal tract. The expression of SATB2 protein is primarily preserved in cancer cells of colorectal origin, indicating that SATB2 could function as a clinically useful diagnostic marker to distinguish colorectal cancer (CRC) from other types of cancer. The aim of this study was to further explore and validate the specific expression pattern of SATB2 as a clinical biomarker and to compare SATB2 with the well-known cytokeratin 20 (CK20). Immunohistochemistry was used to analyze the extent of SATB2 expression in tissue microarrays with tumors from 9 independent cohorts of patients with primary and metastatic CRCs (n=1882). Our results show that SATB2 is a sensitive and highly specific marker for CRC with distinct positivity in 85% of all CRCs, and that SATB2 and/or CK20 was positive in 97% of CRCs. In conclusion, the specific expression of SATB2 in a large majority of CRCs suggests that SATB2 can be used as an important complementary tool for the differential diagnosis of carcinoma of unknown primary origin.

Background: Transanal total mesorectal excision (TaTME) has been proposed as an approach in patients with mid and low rectal cancer. The TaTME procedure has been introduced in the Netherlands in a structured training pathway, including proctoring. This study evaluated the local recurrence rate during the implementation phase of TaTME. Methods: Oncological outcomes of the first ten TaTME procedures in each of 12 participating centres were collected as part of an external audit of procedure implementation. Data collected from a cohort of patients treated over a prolonged period in four centres were also collected to analyse learning curve effects. The primary outcome was the presence of locoregional recurrence. Results: The implementation cohort of 120 patients had a median follow up of 21⋅9 months. Short-term outcomes included a positive circumferential resection margin rate of 5⋅0 per cent and anastomotic leakage rate of 17 per cent. The overall local recurrence rate in the implementation cohort was 10⋅0 per cent (12 of 120), with a mean(s.d.) interval to recurrence of 15⋅2(7⋅0) months. Multifocal local recurrence was present in eight of 12 patients. In the prolonged cohort (266 patients), the overall recurrence rate was 5⋅6 per cent (4⋅0 per cent after excluding the first 10 procedures at each centre). Conclusion: TaTME was associated with a multifocal local recurrence rate that may be related to suboptimal execution rather than the technique itself. Prolonged proctoring, optimization of the technique to avoid spillage, and quality control is recommended.

These data indicate that low expression of LMNA is associated with an increased disease recurrence in stage II and III colon cancer patients, and suggest that these patients in particular may benefit from adjuvant chemotherapy.

BackgroundThe prognostic role of pericolic or perirectal isolated tumor deposits (ITDs) in node-negative colorectal cancer (CRC) patients is unclear. Rules to define ITDs as regional lymph node metastases changed in subsequent editions of the TNM staging without substantial evidence. Aim of this study was to investigate the correlation between ITDs and disease recurrence in stage II and III CRC patients.Materials and MethodsThe medical files of 870 CRC patients were reviewed. Number, size, shape, and location pattern of all ITDs in node-negative patients were examined in relation to involvement of vascular structures and nerves. The correlation between ITDs and the development of recurrent disease was investigated.ResultsDisease recurrence was observed in 50.0% of stage II patients with ITDs (13 of 26), compared with 24.4% of stage II patients without ITDs (66 of 270) (P < .01). Disease-free survival of ITD-positive stage II patients was comparable with that of stage III patients. Also within stage III, more recurrences were observed in ITD-positive patients compared with ITD-negative patients (65.1 vs. 39.1%, respectively). No correlation was found between size of ITDs and disease recurrence. More recurrences were seen in patients with irregularly shaped ITDs compared with patients with 1 or more smooth ITDs present.ConclusionsBecause of the high risk of disease recurrence, all node-negative stage II patients with ITDs, regardless of size and shape, should be classified as stage III, for whom adjuvant chemotherapy should be considered.

Purpose. To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers. Methods. From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, b-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction-based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status. Results. Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P \ 0.01, P = 0.04, and P \ 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and highp53-expressing tumors (P \ 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P \ 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P \ 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9-2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3-5.6) to be independently associated with disease recurrence. Conclusions. p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence.