Olli Carpén

University of Turku, Turku, Varsinais-Suomi, Finland

Are you Olli Carpén?

Claim your profile

Publications (100)486.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Disseminated high-grade serous ovarian cancer (HGS-OvCa) is an aggressive disease treated with platinum and taxane combination therapy. While initial response can be favorable, the disease typically relapses with treatment resistance. As genomic alterations in HGS-OvCa are heterogenous, identification of clinically meaningful molecular markers for outcome prediction is challenging. We developed a novel computational approach (PSFinder) that fuses transcriptomics and clinical data to identify HGS-OvCa prognostic subgroups for targeted treatment. Application of PSFinder to transcriptomics data from 180 HGS-OvCa patients treated with platinum-taxane therapy revealed 61 transcript isoforms that characterize two poor and one good survival associated groups (p = 0.007). These groups were validated in eight independent data sets, including a prospectively collected ovarian cancer cohort. Two poor prognostic groups have distinct expression profiles and are characteristic by increased hypermethylation and stroma related genes. Integration of the PSFinder signature and BRCA1/2 mutation status allowed even better stratification of HGS-OvCa patients' prognosis. The herein introduced novel and generally applicable computational approach can identify outcome-related subgroups and facilitate the development of precision medicine to overcome drug resistance. A limited set of biomarkers divides HGS-OvCa into three prognostic groups and predicts patients in need of targeted therapies. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 06/2015; DOI:10.1158/0008-5472.CAN-14-3242 · 9.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For endometrial carcinoma, prognostic stratification methods do not satisfactory identify patients with adverse outcome. Currently, histology, tumor grade and stage are used to tailoring surgical treatment and to determine the need for adjuvant treatment. Low-risk patients are not considered to require adjuvant therapy or staging lymphadenectomy. For patients with intermediate or high risk, some guidelines recommend tailoring adjuvant treatment according to additional negative prognostic factors. Our objective was to evaluate the biomarker potential of the ASRGL1 protein in endometrial carcinoma. Using The Human Protein Atlas (www.proteinatlas.org), the L-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate. ASRGL1 expression was immunohistochemically evaluated with an extensively validated antibody on two independent endometrial carcinoma cohorts (n=229 and n=286) arranged as tissue microarrays. Staining results were correlated with clinical features. Reduced expression of ASRGL1, defined as <75% positively stained tumor cells, was significantly associated with poor prognosis and reduced disease-specific survival in endometrioid endometrial adenocarcinoma (EEA). In multivariate analysis the hazard ratios for disease-specific survival were 3.55 (95% CI=1.10-11.43; p=0.003) and 3.23 (95% CI=1.53-6.81; p=0.002) in the two cohorts, respectively. Of the 48 cases with grade 3 stage I tumor all disease-related deaths were associated with low ASRGL1 expression. Loss of ASRGL1 in EEA is a powerful biomarker for poor prognosis and retained ASRGL1 has a positive impact on survival. ASRGL1 immunohistochemistry has potential to become an additional tool for prognostication in cases where tailoring adjuvant treatment according to additional prognostic factors besides grade and stage is recommended. Copyright © 2015. Published by Elsevier Inc.
    Gynecologic Oncology 04/2015; 137(3). DOI:10.1016/j.ygyno.2015.03.055 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: All human cells are covered by glycans, the carbohydrate units of glycoproteins, glycolipids, and proteoglycans. Most glycans are localized to cell surfaces and participate in events essential for cell viability and function. Glycosylation evolves during carcinogenesis, and therefore carcinoma-related glycan structures are potential cancer biomarkers. Colorectal cancer is one of the world's three most common cancers, and its incidence is rising. Novel biomarkers are essential to identify patients for targeted and individualized therapy. We compared the N-glycan profiles of 5 rectal adenomas and 18 rectal carcinomas of different stages by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Paraffin- embedded tumor samples were deparaffinized, and glycans were enzymatically released and purified. We found differences in glycosylation between adenomas and carcinomas: monoantennary, sialylated, pauci-mannose and small high-mannose N-glycan structures were more common in carcinomas than in adenomas. We also found differences between stage I-II and stage III carcinomas. Based on these findings, we selected two glycan structures: pauci-mannose and sialyl Lewis a, for immunohistochemical analysis of their tissue expression in 220 colorectal cancer patients. In colorectal cancer poor prognosis correlated with elevated expression of sialyl Lewis a , and in advanced colorectal cancer poor prognosis correlated with elevated expression of pauci-mannose. In conclusion, by mass spectrometry we found several carcinoma related glycans, and we demonstrate a method of transforming these results into immunohistochemistry, a readily applicable method to study biomarker expression in patient samples. Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
    Molecular &amp Cellular Proteomics 12/2014; 14(2). DOI:10.1074/mcp.M114.041632 · 7.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Radiotherapy is a mainstay for treatment of many human cancer types, including head and neck squamous cell carcinoma (HNSCC). Thereby, it is clinically very relevant to understand the mechanisms determining radioresistance. Here, we identify CIP2A as an Oct4 target gene and provide evidence that they co-operate in radioresistance. Oct4 positively regulates CIP2A expression both in testicular cancer cell lines as well as in embryonic stem cells. To expand the relevance of these findings we show that Oct4 and CIP2A are co-expressed in CD24 positive side-population of patient-derived HNSCC cell lines. Most importantly, all Oct4 positive HNSCC patient samples were CIP2A positive and this double positivity was linked to poor differentiation level, and predicted for decreased patient survival among radiotherapy treated HNSCC patients. Oct4 and CIP2A expression was also linked with increased aggressiveness and radioresistancy in HNSCC cell lines. Together we demonstrate that CIP2A is a novel Oct4 target gene in stem cells and in human cancer cell lines. Clinically these results suggest that diagnostic evaluation of HNSCC tumors for Oct4 or Oct4/CIP2A positivity might help to predict HNSCC tumor radioresistancy. These results also identify both Oct4 and CIP2A as potential targets for radiosensitation.
    Oncotarget 12/2014; · 6.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human epididymis protein 4 (HE4) is a novel tumour marker in epithelial ovarian cancer (EOC). Data on its profile and predictive potential for subsequent outcome after neoadjuvant chemotherapy (NACT) are still under investigation. The aim of this study was to compare CA125 and HE4 profiles with radiologic response after NACT and to evaluate their potential as predictors of clinical outcome in a primarily inoperable EOC patient cohort. Twenty-five EOC patients of high-grade subtype (HGSC) treated with NACT were enrolled in the study. Serum HE4 and CA125 samples were taken at the time of diagnosis and before interval debulking surgery (IDS). Pre-NACT and pre-IDS HE4 and CA125 and their percentage changes were compared with NACT response seen on CT and surgical outcome in IDS. We also evaluated the biomarkers' abilities to predict platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). All 25 patients were considered inoperable in laparoscopy at the time of diagnosis. HE4 and CA125 changes during NACT did not correlate with the changes seen on CT. Surgical outcome in IDS was associated with pre-IDS biomarker values but not with those taken before diagnosis. In IDS, 87 % had <1-cm residual tumour. In patients with HE4 change >80 and <80 % during NACT, the median OS was 3.38 and 1.60 years (p = 0.01), respectively. Serum HE4 is a promising additional tool when evaluating advanced HGSC patient's response to NACT. It may be helpful when deciding whether to proceed to IDS or to second-line chemotherapy.
    Tumor Biology 09/2014; 35(12). DOI:10.1007/s13277-014-2553-1 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Basal-like breast carcinomas, characterized by unfavorable prognosis and frequent metastases, are associated with epithelial-to-mesenchymal transition. During this process, cancer cells undergo cytoskeletal reorganization and up-regulate membrane-type-1 matrix metalloproteinase (MT1-MMP, MMP14), which functions in actin-based pseudopods to drive invasion by extracellular matrix degradation. However, the mechanisms that couple matrix proteolysis to the actin cytoskeleton in cell invasion have remained unclear. Based on a yeast two-hybrid screen for the MT1-MMP cytoplasmic tail-binding proteins, we identify here a novel Src-regulated protein interaction between the dynamic cytoskeletal scaffold protein palladin and MT1-MMP. These proteins were coexpressed in invasive human basal-like breast carcinomas and corresponding cell lines, where they were associated in the same matrix contacting and degrading membrane complexes. The silencing and overexpression of the 90-kDa palladin isoform revealed the functional importance of the interaction with MT1-MMP in pericellular matrix degradation and mesenchymal tumor cell invasion, whereas in MT1-MMP negative cells palladin overexpression was insufficient for invasion. Moreover, this invasion was inhibited in a dominant negative manner by an immunoglobulin-domain-containing palladin fragment lacking the dynamic scaffold and Src-binding domains. These results identify a novel protein interaction that links matrix degradation to cytoskeletal dynamics and migration signaling in mesenchymal cell invasion.
    Molecular Biology of the Cell 07/2014; 25(17). DOI:10.1091/mbc.E13-11-0667 · 4.55 Impact Factor
  • European Journal of Cancer 07/2014; 50:S157. DOI:10.1016/S0959-8049(14)50578-3 · 4.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation predicts non-responsiveness, positive predictive markers are not in clinical practice. We previously showed that immunohistochemistry (IHC)-guided EGFR gene copy number (GCN) analysis may identify CRC patients benefiting from anti-EGFR treatment. Here we tested the predictive value of such analysis in chemorefractory metastatic CRC, elucidated EGFR GCN heterogeneity within the tumors, and evaluated the association between EGFR GCN, KRAS status, and anti-EGFR antibody response in CRC cell lines. The chemorefractory patient cohort consisted of 54 KRAS wild-type (WT) metastatic CRC patients. EGFR GCN status was analyzed by silver in situ hybridization using a cut-off value of 4.0 EGFR gene copies/cell. KRAS-WT and KRAS mutant CRC cell lines with different EGFR GCN were used in in vitro studies. The chemorefractory CRC tumors with EGFR GCN increase (≥4.0) responded better to anti-EGFR therapy than EGFR GCN (<4.0) tumors (clinical benefit, P = 0.0004; PFS, HR = 0.23, 95% CI 0.12-0.46). EGFR GCN counted using EGFR IHC guidance was significantly higher than the value from randomly selected areas verifying intratumoral EGFR GCN heterogeneity. In CRC cell lines, EGFR GCN correlated with EGFR expression. Best anti-EGFR response was seen with KRAS-WT, EGFR GCN = 4 cells and poorest response with KRAS-WT, EGFR GCN = 2 cells. Anti-EGFR response was associated with AKT and ERK1/2 phosphorylation, which was effectively inhibited only in cells with KRAS-WT and increased EGFR GCN. In conclusion, IHC-guided EGFR GCN is a promising predictor of anti-EGFR treatment efficacy in chemorefractory CRC.
    PLoS ONE 06/2014; 9(6):e99590. DOI:10.1371/journal.pone.0099590 · 3.23 Impact Factor
  • Clinical Cancer Research 05/2014; 19(19_Supplement):A2-A2. DOI:10.1158/1078-0432.OVCA13-A2 · 8.19 Impact Factor
  • Clinical Cancer Research; 05/2014
  • Clinical Cancer Research 05/2014; 19(19_Supplement):B43-B43. DOI:10.1158/1078-0432.OVCA13-B43 · 8.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inappropriate MET tyrosine kinase receptor signaling is detected in almost all types of human cancer and contributes to malignant growth and MET dependency via proliferative and antiapoptotic activities. Independently, Tensin-4 (TNS4) is emerging as a putative oncogene in many cancer types, but the mechanisms of TNS4 oncogenic activity are not well established. Here, we demonstrate that TNS4 directly interacts with phosphorylated MET via the TNS4 SH2-domain to positively regulate cell survival, proliferation, and migration, through increased MET protein stability. In addition, TNS4 interaction with β1-integrin cytoplasmic tail positively regulates β1-integrin stability. Loss of TNS4 or disruption of MET-TNS4 interaction triggers MET trafficking toward the lysosomal compartment that is associated with excessive degradation of MET and triggers MET-addicted carcinoma cell death in vitro and in vivo. Significant correlation between MET and TNS4 expression in human colon carcinoma and ovarian carcinoma suggests TNS4 plays a critical role in MET stability in cancer.
    Developmental Cell 05/2014; 29(5). DOI:10.1016/j.devcel.2014.03.024 · 10.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Formins are cytoskeleton regulating proteins characterized by a common FH2 structural domain. As key players in the assembly of actin filaments, formins direct dynamic cytoskeletal processes that influence cell shape, movement and adhesion. The large number of formin genes, fifteen in the human, suggests distinct tasks and expression patterns for individual family members, in addition to overlapping functions. Several formins have been associated with invasive cell properties in experimental models, linking them to cancer biology. One example is FMNL1, which is considered to be a leukocyte formin and is known to be overexpressed in lymphomas. Studies on FMNL1 and many other formins have been hampered by a lack of research tools, especially antibodies suitable for staining paraffin-embedded formalin-fixed tissues. Here we characterize, using bioinformatics tools and a validated antibody, the expression pattern of FMNL1 in human tissues and study its subcellular distribution. Our results indicate that FMNL1 expression is not restricted to hematopoietic tissues and that neoexpression of FMNL1 can be seen in epithelial cancer.
    Journal of Histochemistry and Cytochemistry 04/2014; 62(6). DOI:10.1369/0022155414532293 · 2.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stress fibers are major contractile actin structures in non-muscle cells, where they have an important role in adhesion, morphogenesis and mechanotransduction. Palladin is a multidomain protein, which associates with stress fibers in a variety of cell-types. However, the exact role of palladin in stress fiber assembly and maintenance has remained obscure, and whether it functions as an actin filament cross-linker or scaffolding protein was unknown. We demonstrate that palladin is specifically required for assembly of non-contractile dorsal stress fibers, and is consequently essential for generation of stress fiber networks and regulation of cell morphogenesis in osteosarcoma cells migrating in three-dimensional collagen matrix. Importantly, we reveal that palladin is necessary for the recruitment of vasodilator stimulated phosphoprotein (VASP) to dorsal stress fibers, and that it promotes stress fiber assembly through VASP. Both palladin and VASP display similar rapid dynamics at dorsal stress fibers, suggesting that they associate with stress fibers as a complex. Thus, palladin functions as a dynamic scaffolding protein, which promotes the assembly of dorsal stress fibers by recruiting VASP to these structures.
    Journal of Cell Science 02/2014; 127(9). DOI:10.1242/jcs.135780 · 5.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. Eight pathologists from four countries (Sweden, Denmark, Norway and Finland) received an educational lecture on diagnosis of ovarian carcinoma type. All tumour-containing slides from 54 ovarian carcinoma cases were independently reviewed by the participants, who 1) determined type based purely on histology, 2) indicated whether they would apply immunohistochemistry in their routine practice, and 3) determined type after reviewing the staining results. The results for 6 markers (WT1, TP53, P16, HNF-1beta, ARID1A and PR) were determined for all 54 cases, by staining a tissue microarray. The median concordance with central review diagnosis was 86%, significantly improving to 90% with incorporation of immunostaining results (p=0.0002). The median interobserver agreement was 78%, significantly improving to 85% with incorporation of immunostaining results. (p=0.0002). Use of the immunostaining results significantly improved both diagnostic accuracy and interobserver agreement. These results indicate that ovarian carcinoma type can be reliably diagnosed by pathologists from different countries, and further demonstrates that immunohistochemistry has an important role in improving diagnostic accuracy and agreement between pathologists. This article is protected by copyright. All rights reserved.
    Histopathology 12/2013; 64(7). DOI:10.1111/his.12349 · 3.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer cells can obtain their ability to invade and metastasise by undergoing epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular plasticity, malignant cells can remodel their actin cytoskeleton and down-regulate proteins needed for cell-cell contacts. The mechanisms of cytoskeletal reorganisation resulting in mesenchymal morphology and increased invasive potential are poorly understood. Actin nucleating formins have been implicated as key players in EMT. Here, we analysed which formins are altered in squamous cell carcinoma related EMT. FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT. In human tissues FHOD1 was primarily expressed in mesenchymal cells, with little expression in epithelia. However, specimens from oral squamous cell cancers demonstrated consistent FHOD1 upregulation in mesenchymally transformed cells at the invasive edge. This upregulation was confirmed in an oral squamous carcinoma model, where FHOD1 expression was markedly increased upon EMT in a PI3K signalling dependent manner. In the EMT cells FHOD1 contributed to the spindle-shaped morphology and mesenchymal F-actin organization. Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT. In addition, we show that FHOD1 upregulation occurs during cancer cell EMT in vivo, which indicates that FHOD1 may contribute to tumour progression.
    PLoS ONE 09/2013; 8(9):e74923. DOI:10.1371/journal.pone.0074923 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of tumor debulking surgery in the management of epithelial ovarian cancer (EOC), which is often disseminated in the peritoneal cavity at the time of diagnosis, has a significant impact on prognosis. We compared (18)F-fluorodeoxyglucose (FDG) positron emission tomography/contrast-enhanced computed tomography (PET/CT) to contrast-enhanced CT for the detection of dissemination into the abdominal cavity preventing successful primary debulking surgery. Forty-one women with EOC underwent preoperative whole-body low-dose FDG-PET/CT followed by diagnostic high dose contrast-enhanced CT scan, and the results were compared with systematically recorded surgical findings as a reference standard. Both site-based and patient-based analyses were conducted. FDG-PET/CT was superior to conventional CT for the detection of carcinomatosis in subdiaphragmatic peritoneal surfaces (p=0.020) and in the bowel mesentery (p=0.001). Patient-based analysis of upper abdominal areas requiring extensive surgical procedures showed no significant differences between the two imaging methods. The sensitivity of PET/CT and CT was poor in certain areas of the peritoneal cavity (64 % vs. 27% in the small bowel mesentery and 65 % vs. 55 % in the right upper abdomen). Extra-abdominal disease spread was detected by PET/CT in 32 patients and by CT in 25 patients. PET/CT was not superior to CT for the detection of intra-abdominal disease spread. Patients with suspected EOC should be referred for upfront radical surgery regardless of the results of preoperative imaging studies. PET/CT is more effective for the detection of extra-abdominal disease than CT, but the clinical significance of this finding is unclear.
    Gynecologic Oncology 08/2013; 131(2). DOI:10.1016/j.ygyno.2013.08.023 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p < 0.001). High eIF4E expression was associated with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 % CI 1.32-3.00, p = 0.0008) and was in a multivariate analysis an independent prognostic factor. High eIF4E expression was associated with worse outcome also after detection of distant metastasis (HR = 1.88, 95 % CI 1.20-2.94, p = 0.0060). In the subgroup analysis the survival effect was strongest among patients treated with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002), whereas no such effect was seen among patients who had not received anthracycline with significant difference in heterogeneity between the two groups (p = 0.0358). High expression of eIF4E is associated with adverse tumor characteristics and predicts poor breast cancer-specific survival. This effect is emphasized in patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive factor warrants further studies.
    Breast Cancer Research and Treatment 08/2013; 141(1). DOI:10.1007/s10549-013-2671-2 · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: In endometrioid endometrial adenocarcinoma (EEA), the currently established prognostic factors in clinical guidelines are stage and grade. Many guidelines include lymphovascular invasion (LVI) and tumour size as prognostic factors. Although several studies have associated lack of estrogen (ER) and progesterone receptor (PR) expression with reduced outcome, the prognostic use of these markers is uncommon. Better prognostication of clinical behaviour would be useful in patients with early stage (I-II) disease. In this study we evaluated ER and PR as prognostic factors in EEA, and compared their expression with other potential biomarkers and clinical parameters. METHODS: Tissue microarrays were constructed from 182 patients with stage I-II EEA. ER, PR, p53, Ki-67, PTEN, MLH and HER-2 expression was assessed by immunohistochemical staining and HER-2 was confirmed with SISH. The results were correlated with clinicopathologic parameters and to disease-free survival. RESULTS: Eleven patients (6%) developed recurrent disease during a median follow up time of 62.8months. In univariate analysis FIGO grade (p=0.019), positive expression of p53 (p=0.010) and negative PR expression (p=0.001) were associated with a shorter disease-free survival. In multivariate analysis only negative PR expression (p=0.019) was significantly associated with a shorter disease-free survival. LVI and tumour size where not of prognostic value. CONCLUSIONS: Lack of PR expression is a strong, independent risk factor for tumour recurrence in patients with stage I-II endometrioid endometrial cancer. The use of this easily measurable biomarker as a prognostic factors in the clinical context should be considered and tested in a larger patient population.
    Gynecologic Oncology 06/2013; 130(3). DOI:10.1016/j.ygyno.2013.06.015 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) associates with treatment resistance and adverse outcome in several human cancers. We studied ALDH1 expression in rectal cancer, with special emphasis on its association with treatment response and disease outcome. Immunohistochemical staining for ALDH1 was conducted for 64 biopsies and 209 operative samples from rectal cancer patients treated with short- (n = 89) or long-course (n = 46) (chemo)radiotherapy plus surgery, or with surgery only (n = 74). The staining results were compared to clinicopathological variables, tumor regression grade (TRG) and disease outcome. Nuclear β-catenin expression pattern was analyzed from 197 operative samples. Positive ALDH1 expression was present in 149 operative samples (71%), correlating with deficient nuclear β-catenin regulation (P = .018). In a pairwise comparison of respective biopsy and operative samples, ALDH1 expression remained stable or increased after preoperative (chemo)radiotherapy in most of the cases, while it decreased in few cases only (P = .02 for positive/negative category; P <.001 for intensity). ALDH1 expression did not, however, relate to tumor regression grade. In node-negative rectal cancer, ALDH1 expression was an independent predictor of short disease-free and disease-specific survival (P = .044; P = .049), specifically among patients treated with adjuvant chemotherapy. We conclude that ALDH1 associates with deregulated β-catenin signaling, supporting the role of ALDH1 in rectal cancer stemness. ALDH1 expression relates to poor outcome in early stage rectal cancer, a group where new prognostic tools are particularly needed, and may indicate chemo- and radioresistance.
    Human pathology 01/2013; 44(6). DOI:10.1016/j.humpath.2012.10.003 · 2.81 Impact Factor

Publication Stats

3k Citations
486.64 Total Impact Points


  • 2005–2015
    • University of Turku
      • Department of Pathology
      Turku, Varsinais-Suomi, Finland
  • 1981–2012
    • University of Helsinki
      • • Division of Pharmacology and Toxicology
      • • Department of Pathology
      • • Department of Biosciences
      Helsinki, Province of Southern Finland, Finland
  • 2009
    • Turku University Hospital
      Turku, Varsinais-Suomi, Finland
  • 2008
    • Mayo Foundation for Medical Education and Research
      • Department of Neurology
      Scottsdale, AZ, United States
  • 2003–2006
    • Helsinki University Central Hospital
      • Department of Pathology
      Helsinki, Southern Finland Province, Finland
    • Finnish Institute of Occupational Health
      • Centre of Expertise for Health and Work Ability
      Helsinki, Southern Finland Province, Finland
    • Universität Potsdam
      Potsdam, Brandenburg, Germany
  • 1993
    • Karolinska Institutet
      Solna, Stockholm, Sweden