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Biomedical subjects

H Hollema

Publications and source records attributed to H Hollema.

At least 19 recordsLinked to original sources
PubMed2006

EGFR expression is associated with groin node metastases in vulvar cancer, but does not improve their prediction.

OBJECTIVES: High morbidity of elective inguinofemoral lymphadenectomy in early stage vulvar cancer patients urges the need for defining a group of low-risk patients in whom inguinofemoral lymphadenectomy can be safely omitted. Aim of the study was to evaluate whether in addition to 'classic' clinicopathological factors determination of EGFR expression in vulvar cancer can be helpful in defining such a 'low-risk' group. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples of 197 surgically treated T1/2 patients were collected in a Tissue Micro Array (TMA). On this TMA, immunohistochemistry for EGFR was performed. Logistic regression analyses were performed including histopathological characteristics with the presence of nodal metastases as outcome. A predictive model was constructed, and absolute risks were calculated. RESULTS: EGFR expression was present in 68% of the vulvar tumors and related to the presence of lymph node metastases (OR 2.12, 95% CI 1.09-4.10). Our predictive model with only clinicopathological factors was able to define a group of patients with a likelihood of absence of lymph node metastases of 13% (95% CI 5-36), which could be decreased to 6% (95% CI 0-29) after inclusion of EGFR expression (p=0.07). CONCLUSIONS: EGFR expression is present in the majority of vulvar tumors and is associated with groin node metastases in vulvar cancer. Current classic clinicopathological predictive factors for inguinofemoral lymph node metastases with or without EGFR analysis are not strong enough for identification of "sufficiently low" risk T1/2 vulvar cancer patients. Our predictive model approach however is excellent for evaluation of new cell biological parameters, associated with clinical outcome.

Adult↗
PubMed2006

Factors influencing p53 expression in ovarian cancer as a biomarker of clinical outcome in multicentre studies.

The prognostic impact of p53 immunostaining in a large series of tumours from epithelial ovarian cancer patients in a two-centre study was analysed. The study population (n=476) comprised of a retrospective series of 188 patients (Dutch cohort) and a prospective series of 288 patients (Scottish cohort) enrolled in clinical trials. P53 expression was determined by immunohistochemistry on tissue microarrays. Association with progression-free survival (PFS) and overall survival (OS) was analysed by univariate and multivariate Cox regression analysis. Aberrant p53 overexpression was significantly associated with PFS in the Dutch and Scottish cohorts (P=0.001 and 0.038, respectively), but not with OS in univariate analysis. In multivariate analysis, when the two groups were combined and account taken of clinical factors and country of origin of the cohort, p53 expression was not an independent prognostic predictor of PFS or OS. In this well-powered study with minimal methodological variability, p53 immunostaining is not an independent prognostic marker of clinical outcome in epithelial ovarian cancer. The data demonstrate the importance of methodological standardisation, particularly defining patient characteristics and survival end-point data, if biomarker data from multicentre studies are to be combined.

Adult↗
PubMed2006

Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer.

BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. AIM: To analyse the value of family history, microsatellite instability (MSI) analysis and MMR protein staining in the tumour to predict the presence of an MMR gene mutation in such patients. METHODS: In 281 patients diagnosed with CRC before the age of 50 years or with CRC and at least one additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex ligation-dependent probe amplification. MSI analysis with five consensus markers and MMR protein staining for MLH1, MSH2 and MSH6 were carried out in the tumours. RESULTS: 25 pathogenic mutations (8 in MLH1, 9 in MSH2 and 8 in MSH6) were found. MSI analysis missed three and immunohistochemistry (IHC) missed two mutation carriers. Sensitivities of family history, MSI analysis and IHC for the presence of a mutation were 76%, 82% and 88%, specificities were 64%, 70% and 84%, and positive predictive values were 19%, 23% and 38%, respectively. Multivariate analysis showed the highest odds ratio for IHC (38.3, 95% confidence interval 9.0 to 184). Prevalence of pathogenic germline MMR gene mutations in patients with CRC before the age of 50 years was 6% and in those with > or =2 HNPCC-associated tumours was 22%. In the second group, no mutation carriers were found among the 29 patients who were diagnosed with their first tumour after the age of 60 years. CONCLUSION: Family history, MSI analysis and IHC are indicative parameters to select patients with CRC for MMR gene mutation analysis. The data show that IHC is the best single selection criterion.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Cell cycle regulators and apoptosis-associated proteins in relation to proliferative activity and degree of apoptosis in HNPCC versus sporadic endometrial carcinoma.

AIMS: Mismatch repair gene malfunction occurs early in the carcinogenesis of hereditary non-polyposis colorectal cancers (HNPCCs), leading to an accelerated accumulation of mutations and possibly to change in expression of cell cycle proteins. There is strong evidence that tumorigenesis in HNPCCs differs from sporadic ones. HNPCC-related endometrial cancers are less well studied. Our aim was to compare expression of cell cycle and apoptosis-related proteins in relation to proliferation and apoptosis in HNPCC-related and sporadic endometrial cancers to identify differences in their carcinogenetic pathways. METHODS AND RESULTS: Eighteen HNPCC-related endometrial cancers, each matched by tumour type, stage and grade with two sporadic endometrial cancers, were examined for proliferation, apoptosis and the expression of oestrogen and progesterone receptors, cyclin B1, D3 and E, p21, p27, bcl-2, bax, p53 and COX-2. No differences in proliferation or apoptotic indices were detected between HNPCC-related and sporadic endometrial cancers. Cyclin B1 expression was significantly higher in HNPCC-related cancers than in sporadic endometrial cancers. More HNPCC-related endometrial cancers had total loss of bax expression. CONCLUSIONS: Apart from differences in cyclin B1 and bax expression, HNPCC-related and sporadic endometrial cancers are comparable. The subtle differences detected are consistent with the minor clinical diversity between HNPCC-related and sporadic endometrial cancers.

Adenocarcinoma↗
PubMed2006

Aromatase in the context of breast and endometrial cancer. A review.

Generally, estrogens are considered to be involved in the neoplastic transformation of endometrium. After the menopause these estrogens mainly originate from conversion of adrenal androgens by aromatization in body fat. However, in case of stromal hyperplasia of the ovaries, it cannot be excluded that production of aromatizable androgens by postmenopausal ovaries leads to increased availability of androgen precursors for intratumoral estrogen synthesis in the endometrial tissue as well. The local presence of androgens and the local expression and activity of aromatase is considered important for this steroidogenesis. In this review, we will discuss the available evidence that androgens, produced in hyperplastic ovarian stroma or body fat tissues, play a role in the development of endometrial cancer through conversion into estrogens, a reaction catalyzed in the endometrium by the enzyme aromatase cytochrome P450. As the presence of aromatase appeared to be a pathophysiological factor in the formation of breast cancer, the latter will be evaluated in relation to the development of endometrioid endometrial cancer as well, since both disorders appear partly estrogen dependent. As treatment with aromatase inhibitors appeared feasible in breast cancer, current knowledge of comparable treatment modalities in hormone dependent endometrial cancer will be reviewed.

Adipose Tissue↗
PubMed2005

Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase protein expression on survival in adjuvantly treated stage III colon cancer patients.

BACKGROUND: The predictive value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression on long-term survival by influencing 5-fluorouracil (5-FU) effect were determined in primary tumours and node metastases of stage III colon cancer patients treated adjuvantly with 5-FU regimens (n=391). The effect of TP 53 mutation status, which is thought to be functionally linked to TS inhibition, was also examined. PATIENTS AND METHODS: TS and DPD protein expression was determined by immunohistochemical analysis using tissue microarrays of these colon tumours. Two hundred and twenty tumours had already been screened in a previous study for TP 53 mutations. RESULTS: Low TS protein levels in primary stage III colon tumours appeared to be associated with mucinous histology and low DPD protein levels with young age at time of randomisation. Concordance between TS and DPD expression in primary and metastatic tumours was low. No associations were found between disease-free survival (DFS) and TS or DPD protein levels. When stratified by TP 53 mutation status DFS did not differ with TS expression. CONCLUSIONS: Expression of TS and DPD proteins is not predictive for survival in patients with stage III colon cancer treated adjuvantly with 5-FU regimens. TS protein levels did not alter the effect of TP 53 mutation status.

Age of Onset↗
PubMed2005

Presentations of endometrial activity after curative radiotherapy for cervical cancer.

OBJECTIVES: The treatment of choice for patients with advanced stage cervical cancer is (chemo)radiotherapy. Gynaecologic side effects consist of loss of ovarian function and destruction of the endometrium, resulting in infertility and premature ovarian failure. In premenopausal patients estrogens are prescribed to prevent climacteric symptoms. In general, no progestagens are added to the hormone replacement therapy because of the assumption of complete destruction of the basal layer of the endometrium after pelvic radiotherapy. The aim of this report is to show the different presentations of endometrial activity after curative radiotherapy in patients with cervical cancer. METHODS: Presentation of four patients who developed symptoms of residual endometrial activity. RESULTS: In two patients, proliferation of functional endometrium led to hematocolpos and hematometrum with abdominal pain. The third patient underwent ovarian transposition and developed regular periods 3 months after finishing the radiotherapy. The fourth patient underwent trachelectomy with radiotherapy because of narrow tumour free margins. She developed vaginal blood loss after starting estrogens. CONCLUSIONS: These patients show that in premenopausal patients, curative radiotherapy until 80Gy, may lead to symptoms of residual functional endometrium, e.g. hematometrum, hematocolpos, (ir)regular vaginal blood loss. In our opinion patients should be advised to use estrogens in combination with a progestogen, instead of unopposed estrogens, to prevent stimulation of residual functional endometrium. Tibolone may be an appropriate alternative hormone replacement therapy especially with the advantage of low androgen effects which might support the sexual functions, and the decrease of breast density.

Adult↗
PubMed2005

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. Paraffin embedded material of all retrieved lymph nodes in these patients were serially sectioned and analysed by one pathologist after H & E examination for the presence of micrometastases by IHC. RESULTS: In 60 resection specimens initially staged as pN0 a total of 524 lymph nodes were available for IHC analyses. Micrometastases were detected in 126 out of 524 lymph nodes (24%), corresponding with 18 of the 60 patients (30%) who were upstaged by this technique. Compared with the pN0 group, the disease free survival (DFS) was significantly lower in patients with nodal involvement at IHC (p<0.001). Survival of patients with IHC identified micrometastatic disease was comparable to those with H & E positive lymph nodes. CONCLUSIONS: Micrometastases in regional nodes were detected by cytokeratin-specific IHC in 30% of radical resected GEJ tumours without overt nodal involvement. Their presence conveys a worse prognosis with a significant reduced DFS, suggesting that the finding of micrometastases should be included in the staging system.

Adult↗
PubMed2005

Death receptors and ligands in cervical carcinogenesis: an immunohistochemical study.

OBJECTIVE: Increasing imbalance between proliferation and apoptosis is important in cervical carcinogenesis. The death ligands FasL and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis by binding to their cognate cell-surface death receptors Fas or death receptor (DR) 4 and DR5. This study aims to examine if changes in death ligand and death receptor expression during different stages of cervical carcinogenesis are related to an imbalance between proliferation and apoptosis. METHODS: The immunohistochemical expression and localization of Fas/FasL and DR4/DR5/TRAIL were assessed in 11 normal cervices, 15 cervical intraepithelial neoplasia (CIN) grade I, 15 CIN II, 13 CIN III, and 25 (microinvasive) squamous cell cervical cancers. The number of apoptotic cells was determined by morphological criteria and the number of proliferating cells by counting Ki-67-positive cells. RESULTS: A marked increase in proliferation as well as apoptosis percentage was found with increasing severity of neoplasia. In normal cervix and CIN I samples, FasL, DR4, DR5, and TRAIL staining was mainly observed in the basal/parabasal layer, whereas Fas staining was localized in the superficial, more differentiated epithelial layer. Frequency of Fas-positive staining decreased with increasing severity of CIN. In contrast, homogeneous FasL, DR4, DR5, and TRAIL expression throughout the lesions was more frequently observed in CIN III and cervical cancer. FasL, DR4, DR5, and TRAIL staining patterns were correlated, although TRAIL expression was more intense in low-grade lesions. No association was found between death receptor or ligand expression with the percentage of apoptosis or proliferation. CONCLUSION: The loss of Fas and the deregulation of FasL, DR4, DR5, and TRAIL in the CIN-cervical cancer sequence suggest a possible functional role of these death ligands and receptors during cervical carcinogenesis. The frequent expression of DR4 and DR5 presents these receptors as promising targets for innovative therapy modalities in cervical cancer.

Apoptosis↗
PubMed2004

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. METHODS: Human ovarian tissue was brought into suspension by mechanical and enzymatic treatment. Cells of the MCF-7 breast cancer cell line and activated human lymphocytes were co- incubated for 4 h with or without BIS-1 and with or without ovarian suspension. After incubation, MCF-7 cell death and cell growth were evaluated by fluorescent cell detection and MTT assay, respectively. Ovarian tissue morphology was evaluated immunohistochemically. RESULTS: MCF-7 cell death and cell growth inhibition increased with increasing ratios of lymphocytes to MCF-7 cells. BIS-1 addition gave further augmentation, with a maximum depletion of growing MCF-7 cells of 89% (SD 11%) versus without BIS-1, 23% (SD 15%; P < 0.001). Follicles remained morphologically intact. CONCLUSIONS: Purging of added epithelial tumour cells from ovarian tissue with BIS-1 is possible in vitro. Morphologically, follicles remain intact after this procedure. This method may contribute to safer replacement of ovarian tissue in female cancer survivors.

Adolescent↗
PubMed2004

The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours.

The drug-efflux pumps P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are present in the blood-testis barrier (BTB) and may hamper the delivery of cytotoxic drugs to the testis. The precise localisation of P-gp and MRP1 in testicular tissue and the presence of the efflux pumps MRP2 and breast cancer resistance protein (BCRP) in the BTB are unknown. We therefore studied the localisation of these pumps in the BTB in normal testis (n = 12), in non-seminoma (n = 10) seminoma (n = 10), and testicular lymphoma (n = 9). Slides were scored semi-quantitatively for P-gp, MRP1, MRP2 and BCRP and blood vessels with factor VIII antibody. In normal testis, P-gp and BCRP were strongly expressed by myoid cells and luminal capillary endothelial wall and P-gp also by Leydig cells. MRP1 was observed at the basal side of Sertoli cells and on Leydig cells. MRP2 was only weakly expressed by myoid cells. Seminomas and non-seminomas expressed P-gp and/or BCRP and/or MRP1, lymphomas strongly expressed P-gp, weakly expressed BCRP and did not or showed weak expression of MRP1. There was very little staining for MRP2 in the tumours. Newly formed vessels in all tumours only expressed P-gp and BCRP. P-gp, BCRP and MRP1 are present in different cell layers of the normal testis, suggesting the optimal protection of spermatogenesis. In germ cell tumours, this expression pattern may explain the chemoresistance observed to P-gp, BCRP and MRP1 substrates. In germ cell tumours and testicular lymphomas, P-gp and BCRP expression by tumour cells and by newly formed vessels may also contribute to chemoresistance. These findings underscore the importance of removing the affected testis in cases of primary germ cell tumours and testicular lymphomas, irrespective of whether the patient has already undergone chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Chemotherapy induces death receptor 5 in epithelial ovarian carcinoma.

OBJECTIVES: Defects in the apoptotic pathway are a general cause for drug resistance. Chemotherapy in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has proven to be an effective strategy to induce apoptosis in vitro in ovarian tumor cells. Systemic TRAIL administration might be a therapeutic option, since no toxicity was observed in nonhuman primates. In the present study, expression of TRAIL and its apoptosis-inducing death receptors (DR4 and DR5) and inhibitory decoy receptor (DcR1) was studied in normal ovaries and in malignant ovarian tumors before and after chemotherapy to investigate the therapeutic potential of TRAIL. METHODS: DR4, DR5, DcR1, and TRAIL were studied immunohistochemically in 5 normal ovaries, 15 stages I/II, and 26 stages III/IV primary ovarian cancers, including 19 paired tumor samples (pre- and post-chemotherapy). RESULTS: Surface epithelium of normal ovaries expressed TRAIL and its receptors; ovarian stromal cells expressed only DcR1. Of the ovarian cancers, 73% expressed DR4, 51% DR5, 46% DcR1, and 34% TRAIL. Most primary ovarian cancers (88%) expressed at least one death receptor. TRAIL expression was lower in stage III/IV than in stage I/II tumors (P<0.05). In paired samples, DR5 immunostaining was more frequently (P=0.05) and stronger (P<0.01) expressed in residual tumors. CONCLUSION: Early stage tumors expressed TRAIL more frequently than advanced stage tumors. Most primary and residual ovarian tumors expressed at least one TRAIL death receptor, while in residual tumors following chemotherapy, DR5 was more frequently expressed. Therefore, human recombinant TRAIL administration might be an interesting treatment option.

Apoptosis Regulatory Proteins↗
PubMed2004

Pitfalls in the sentinel lymph node procedure in vulvar cancer.

OBJECTIVES: There is an increasing interest among gynecologic oncologists to implement the sentinel lymph node (SLN) procedure in vulvar cancer patients in clinical practice. However, the safety of this promising method of staging still has to be proven in a randomized trial. MATERIALS AND METHODS: Two vulvar cancer patients are reported to illustrate pitfalls in the sentinel lymph node procedure. RESULTS: The phenomena of bypassing the sentinel lymph node and confusion about the number of removed sentinel lymph nodes are presented and discussed. CONCLUSION: Gynecological oncologists who perform the sentinel lymph node procedure in vulvar cancer patients should perform this technique by following a strict protocol and within the protection of a clinical trial.

Aged↗
PubMed2004

Assessment of apoptosis by M30 immunoreactivity and the correlation with morphological criteria in normal colorectal mucosa, adenomas and carcinomas.

AIMS: To investigate the monoclonal antibody M30 for the assessment of apoptosis in colorectal tissues. Although Terminal deoxyribonucleotidyl transferase mediated nick end labelling (TUNEL) and in-situ end labelling (ISEL) are the methods most often used to demonstrate and quantify apoptosis in histological tissue sections, the interpretation and specificity of these techniques have been controversial. Immunohistochemistry using the monoclonal antibody M30 that recognizes caspase-cleaved cytokeratin 18 is considered to be a promising alternative but has yet to be validated against a generally accepted standard. METHODS AND RESULTS: Paraffin sections of normal colonic mucosa (n = 30), normal mucosa obtained from resection margins from carcinomas (n = 30), colorectal adenomas (n = 84) and carcinomas (n = 40) were studied. Apoptosis of epithelial cells was assessed by M30 immunoreactivity and morphological criteria and expressed as a proportion of the total number of cells counted (apoptotic index). Mean apoptotic indices using M30 were 0.18 +/- 0.04% in normal mucosa, 0.42 +/- 0.04% in adenomas and 1.97 +/- 0.24% in carcinomas. Using morphological criteria, these indices were 0.23 +/- 0.03%, 0.62 +/- 0.06% and 1.78 +/- 0.19%, respectively. Apoptotic counts were higher in normal mucosa obtained from resection margins than in genuinely normal mucosa using the M30 antibody. Apoptotic indices obtained by M30 immunoreactivity and morphological criteria were positively correlated (r = 0.71, P < 0.01). CONCLUSION: Assessment of apoptotic cells by M30 immunoreactivity correlates well with morphological criteria. Apoptotic indices increase in the course of the adenoma-carcinoma sequence. Apoptosis in normal mucosa obtained from resection margins differs from genuinely normal mucosa necessitating caution when interpreting studies of apoptosis in normal colonic mucosa. Our findings support the use of the M30 method in the study of apoptosis in colorectal tissues.

Adenocarcinoma↗
PubMed2003

[The effects of tamoxifen on the female genital tract].

Tamoxifen has both agonistic and antagonistic effects on the female genital tract, depending on the ambient oestradiol concentration and the menopausal status of the patient. In postmenopausal women tamoxifen has an oestrogen agonistic effect on the vaginal epithelium, the uterine myometrium and the endometrium. It may induce benign cystic hyperplasia of the endometrial stroma and cause an increase in poly formation. The risk of endometrial cancer increases 2-3-fold after an exposure of up to 5 years. In asymptomatic tamoxifen users, gynaecological surveillance is not recommended. However, if there is postmenopausal bleeding, then transvaginal ultrasonography and histology of the endometrium are indicated. Tamoxifen can aggravate hot flushes and have a negative effect on sexual function. In premenopausal women, tamoxifen may induce ovarian cysts resulting in high serum-oestradiol levels. Oligomenorrhoea and amenorrhoea will occur in half of the patients. Tamoxifen has an antagonistic effect on the endometrium in premenopausal women and is associated with hot flushes and impaired sexual functioning. Teratogenic effects on the foetus have been described. Despite its gynaecological side effects, the benefits of tamoxifen in breast-cancer treatment outweigh the risks. Patients need to be informed about these side effects. Irregular or postmenopausal blood loss must always be reported to the treating physician.

Breast Neoplasms↗
PubMed2003

Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their histological type and grade.

The biological behaviour of different histological types and grades of soft tissue sarcomas (STS) varies. This might result in a differing sensitivity to cytotoxic drugs. Cross-resistance to functionally and structurally distinct natural-product drugs, known as multidrug resistance (MDR), is associated with the overexpression of P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP). The purpose of this study was to evaluate the expression of P-gp, MRP1 and LRP in STS according to their histological type and grade. In 141 chemotherapy-naive STS patients, the expression of the three MDR proteins was detected by immunohistochemistry. Nine histological types were documented. These were 19% grade 1, 34% grade 2 and 47% grade 3 tumours. Expression of P-gp and LRP was observed more frequently than the expression of MRP1 (P<0.0001). P-gp expression was most pronounced in malignant fibrous histiocytoma (MFH), but was low in leiomyosarcomas. MRP1 was expressed in most malignant peripheral nerve sheath tumours (MPNST). LRP was strongly expressed in MFH and unspecified sarcomas, but was low in liposarcomas. MRP1 and LRP expression was significantly more common in grades 2 and 3 compared with grade 1 tumours. P-gp expression was correlated with MRP1, especially in grade 3 STS. In conclusion, P-gp, MRP1 and LRP are expressed in the majority of STS, but this expression varies according to the histological type. MRP1 and LRP, but not P-gp expression, were found to be correlated to tumour grade. MDR might contribute to the observed differences in clinical behaviour within the heterogeneous group of STS.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2003

Changes in apoptosis during the development of colorectal cancer: a systematic review of the literature.

The development of colorectal cancer is characterised by an accumulation of molecular genetic alterations causing disorders in cell growth, differentiation and apoptosis. Although changes in apoptosis with colorectal cancer development have been studied extensively, a clear consensus of opinion has not yet emerged. In this review, the literature about changes in the frequency and distribution of apoptosis in tissue sections of normal and neoplastic colorectal tissues was reviewed systematically. Using a PUBMED search, 53 relevant articles were identified. Data from these studies are discussed with respect to the following aspects: methods used to detect apoptotic cell death; frequency and locoregional distribution of apoptosis in normal mucosa, adenomas and carcinomas; the correlation between levels of apoptosis and proliferation and the prognostic significance of the degree of apoptosis in colorectal cancer. Possible underlying mechanisms of dysregulation of apoptosis are discussed briefly. Finally, possible therapeutic implications of knowledge of the molecular regulation of apoptosis are discussed and potential options for further research are suggested.

Adenocarcinoma↗