Background: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of... Show moreBackground: Optimal discrimination between leukemic blasts and normal B-cell precursors (BCP) is critical for treatment monitoring in BCP acute lymphoblastic leukemia (ALL); thus identification of markers differentially expressed on normal BCP and leukemic blasts is required.Methods: Multicenter analysis of CD73, CD86 and CD304 expression levels was performed in 282 pediatric BCP-ALL patients vs. normal bone marrow BCP, using normalized median fluorescence intensity (nMFI) values.Results: CD73 was expressed at abnormally higher levels (vs. pooled normal BCP) at diagnosis in 71/108 BCPALL patients (66%), whereas CD304 and CD86 in 119/202 (59%) and 58/100 (58%) patients, respectively. Expression of CD304 was detected at similar percentages in common-ALL and pre-B-ALL, while found at significantly lower frequencies in pro-B-ALL. A significant association (p = 0.009) was found between CD304 expression and the presence of the ETV6-RUNX1 fusion gene. In contrast, CD304 showed an inverse association with MLL gene rearrangements (p = 0.01). The expression levels of CD73, CD86 and CD304 at day 15 after starting therapy (MRD15) were stable or higher than at diagnosis in 35/37 (95%), 40/56 (71%) and 19/41 (46%) cases investigated, respectively. This was also associated with an increased mean nMFI at MRD15 vs. diagnosis of + 24 and +3 nMFI units for CD73 and CD86, respectively. In addition, gain of expression of CD73 and CD86 at MRD15 for cases that were originally negative for these markers at diagnosis was observed in 16% and 18% of cases, respectively. Of note, CD304 remained aberrantly positive in 63% of patients, despite its levels of expression decreased at follow-up in 54% of cases.Conclusions: Here we show that CD73, CD86 and CD304 are aberrantly (over)expressed in a substantial percentage of BCP-ALL patients and that their expression profile remains relatively stable early after starting therapy, supporting their potential contribution to improved MRD analysis by flow cytometry. Show less
While histopathologic assessment of lymph nodes is a core element of colorectal cancer staging algorithms, the prognostic value of lymph node metastases is restricted. This highlights the need... Show moreWhile histopathologic assessment of lymph nodes is a core element of colorectal cancer staging algorithms, the prognostic value of lymph node metastases is restricted. This highlights the need for approaches that detect occult tumor cells and define their prognostic value, to identify colorectal cancer patients who derive the greatest benefit from therapy. In an attempt to gain insights into prognosis in CRC, this thesis focuses on factors that play a role in the detection or behaviour of occult tumor cells. Especially clinical, pathological and molecular factors of CRC will here be discussed. Show less
Quality of surgical procedures in the treatment of cancer patients is of utmost importance. This thesis focuses on two large prospective randomised trials on gastric and rectal cancer. Important... Show moreQuality of surgical procedures in the treatment of cancer patients is of utmost importance. This thesis focuses on two large prospective randomised trials on gastric and rectal cancer. Important feature in both trials was the standardisation and quality control of surgery, enabling the reliable assessment of the rol of adjunctive therapies. The trial on gastric cancer showed no benefitit of extensive lymph node dissection in gastric cancer. However, if postoperative morbidity is reduced, extended surgery may be of benefit. Various ways of reducing the likelihood of postoperative complications are considered. The trial on rectal cancer patients showed that short term preoperative radiotherapy is capable of reducing the risk of local recurrence, which however does not lead to improvement of survival. Moreover, there are important side effects of radiotherapy, the most important one being the increased incidence of fecal incontinence in irradiated patients. Show less
