Mismatch repair protein expression in Amsterdam II criteria-positive patients in Taiwan

Background:

Hereditary non‐polyposis colorectal cancer (HNPCC) is characterized genetically by germline mutations in DNA mismatch repair (MMR) genes. Immunohistochemistry (IHC) has high sensitivity and specificity for identifying MMR‐deficient tumours. This study investigated the clinical presentations and frequency of HNPCC in Taiwan by combined Amsterdam II criteria (AC‐II) and IHC.

Methods:

In 1995–2003, 7108 patients with primary colorectal cancer registered in Chang Gung Memorial Hospital's Colorectal Cancer Registry were screened using AC‐II. Tumour specimens were analysed for MMR protein expression by IHC, and relevant clinicopathological details were documented.

Results:

Some 83 patients fulfilled the AC‐II. Clinicopathologically, 43 patients (52 per cent) had proximal tumours, ten (12 per cent) had poorly differentiated cancers, 17 (20 per cent) had mucinous adenocarcinoma and 51 (61 per cent) had stage I–II tumours. Seventeen patients developed second primary colonic and extracolonic cancers over a mean 7·2‐year follow‐up. Immunohistochemically, 58 patients were MMR protein deficient. They had a significantly earlier age of onset (P < 0·001), more proximal tumour location (P = 0·002), less advanced tumour stage (P = 0·008) and more second primary cancers (P = 0·017) compared with MMR‐competent patients.

Conclusion:

These data show significant differences in clinical features between MMR protein‐deficient and MMR competent subgroups. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

The effect of a screening programme on the outcome of colorectal cancer

Aim The study aimed to determine whether the introduction of a screening programme for colorectal cancer influenced resection and recurrence rates and prognosis. Method Details of patients with a biopsy‐confirmed diagnosis of colorectal cancer attending from January 2002 to December 2006 were entered into a prospective database. All were followed to death or the end of the study period (December 2008). Patients with a synchronous cancer were excluded from analysis. A comparison was made between screen and non‐screen detected cancers for survival, disease‐free survival, location of the primary tumour, resection and recurrence rates. Results In all, 841 [median age 72 (30–101) years; 53% men] patients with colorectal cancer were identified. Of these 68 were screen detected of whom 63 underwent surgery. Screen detected cancers were significantly less advanced at presentation (P = 0.001). There was no significant difference in primary tumour location between screen and non‐screen detected cancers (P = 0.184). Among curative resections, significantly fewer screened compared with non‐screened cancers developed a recurrence [6/59 (10.2%) vs 105/491 (21.4%), P = 0.043]. The mean disease‐free survival for screen and non‐screen detected cancers was 78.3 and 65.0 months (P = 0.010). Overall mean survival was significantly improved for screened (73.8 months) over non‐screened (57.9 months) detected cancers, P = 0.001. Conclusion Screening for colorectal cancer in this population significantly improved overall cancer‐related and disease‐free survival, possibly as a result of the detection of significantly more early staged cancers.     

The relationship between tumour site,clinicopathological characteristics and cancer‐specific survival in patients undergoing surgery for colorectal cancer

Aim It is recognised that colorectal cancer may arise from different genomic instability pathways. There is evidence to suggest that colon and rectal cancers exhibit different clinicopathological features. We examined the relationship between tumour site, clinicopathological characteristics and cancer‐specific survival in patients undergoing potentially curative resection for colorectal cancer. Method Four hundred and eleven patients who underwent surgery. Clinicopathological data including components of the Peterson index, Klintrup scores, haemoglobin and the modified Glasgow Prognostic Score (mGPS) were studied. Results There were 134 (33%) right sided, 125 (30%) left sided and 152 (37%) rectal tumours. Emergency presentation (P < 0.001), anaemia (P < 0.001), higher mGPS (P < 0.001), advanced T stage (P < 0.001), poor differentiation (P < 0.001) and older age (P < 0.05) were more commonly observed in right sided cancer. The mean follow‐up was 94 months (minimum 36 months) and 114 patients died of cancer. There was no difference between tumour site and survival (P = 0.427). On multivariate analysis older age (P = 0.015), lymph node ratio (P < 0.001), mGPS (P = 0.028), Peterson Index (P < 0.001) and Klintrup score (P = 0.008) were independently related to cancer‐specific survival. Klintrup score was only associated with poor cancer‐specific survival in rectal cancer (P = 0.009). Conclusion The study suggests that colorectal cancer is a group of heterogeneous tumours with different clinicopathological features. Despite this, there was no difference between tumour site and survival. The prognostic role of clinicopathological factors in tumours arising from different genomic instability pathways requires further study.     

Mechanisms of Hypothermic Machine Perfusion to Decrease Donation After Cardiac Death Graft Inflammation: Through the Pathway of Upregulating Expression of KLF2 and Inhibiting TGF‐β Signaling

Hypothermic machine perfusion (HMP) has been known as an efficient way to improve kidney graft function, but the underlying mechanisms remain unclear. Here, we adopt a rabbit reperfusion mode to investigate the upstream mechanisms of end‐ischemic HMP of kidneys from donors after cardiac death (DCD), with static cold storage (CS) as a control. Eighteen New Zealand healthy male rabbits (12 weeks old, with a weight of 3.0 ± 0.2 kg) were randomly divided into three groups: HMP group, CS group, and Normal group (n = 6). The left kidney of rabbits underwent warm ischemia for 25 min through clamping the left renal pedicle and then reperfusion for 1 h. Then the left kidneys were preserved by CS or HMP (4°C for 4 h) ex vivo respectively, after they were autotransplanted and rabbits were submitted to a right nephrectomy. Twenty‐four hours after reperfusion, all left renal specimens were collected. Finally, the expression of Krüppel‐like factor 2 (KLF2), transforming growth factor‐β (TGF‐β) and SMAD4 protein in renal cortical tissue were detected by immunoblotting, and the TGF‐β and SMAD4 expressions were further confirmed by immunohistochemistry analysis. We found that expression of KLF2 in HMP group was significantly higher than CS group (P = 0.011), while expression of TGF‐β and SMAD4 in HMP group were significantly lower than CS group (P = 0.002, P = 0.01, respectively); Compared with normal group, the expression of TGF‐β and SMAD4 in HMP and CS group significantly increased (P<0.05). Compared with CS group, TGF‐β and SMAD4 protein were equally down‐regulated in glomerular and the tubular epithelial cells in HMP group confirmed by immunohistochemistry. In conclusion, HMP may decrease DCD kidneys inflammation through the pathway of upregulating expression of KLF2 and inhibiting TGF‐β signaling after transplantation.     

Association between interleukin‐4R and TGF‐β1 gene polymorphisms and the risk of colorectal cancer in a Korean population

Aim Colorectal cancer is associated with inflammatory bowel disease. The mechanisms of how different genetic make‐ups of cytokines might influence the individual susceptibility to develop particular types of tumours are still unknown. The authors analysed the association between genetic polymorphisms in cytokine/cytokine receptor genes and the risk of colorectal cancer in a Korean population. Method The authors assessed polymorphisms of the interleukin: IL‐1, IL‐1R, IL‐2, IL‐4, IL‐4R, IL‐10, transforming growth factor (TGF)‐β1, IFN‐γ genes in Korean patients with colorectal cancer (n = 170) and in a normal healthy control group (n = 130) to investigate the association between theses cytokine gene polymorphisms and the risk of colorectal cancer. Results The IL‐4R 1902*T allele was found to be associated with an increased risk of colon cancer (P < 0.01, OR = 2.0) and rectal cancer (P < 0.05, OR = 1.8). The IL‐4R 1902*C allele was associated with a decreased risk of both colon cancer (P < 0.01, OR = 0.51) and rectal cancer (P < 0.05, OR = 0.5). The TFG‐β1 10*T allele was found to be associated with an increased risk of colon cancer (P < 0.00, OR = 2.3) and the TFG‐β1 10*C allele with a decreased risk of colon cancer (P < 0.00, OR = 0.43). Conclusion These results suggest that the genetic polymorphisms of IL‐4R and TGF‐β1 are associated with the risk of colorectal cancer in a Korean population.     

−509C>T polymorphism in the TGF‐β1 gene promoter is not associated with susceptibility to and progression of colorectal cancer in Chinese

Aim Colorectal cancer is common, accounting for nearly 10% of all cancers. Transforming growth factor‐β1 (TGF‐β1) is a pleiotropic cytokine that has been implicated in the pathogenesis of colorectal neoplasia. The most studied −509C>T polymorphism of TGF‐β1 gene has been associated with various kinds of cancer. This study investigated the association between this genetic variant and the risk and/or progression of colorectal cancer. Method A case–control study was carried out of 150 colorectal cancer cases and 503 healthy controls. DNA was extracted from blood cell nuclear materials, and −509C>T polymorphism in the TGF‐β1 gene promoter was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Colorectal cancer tissues (n = 70) were obtained from the studied cases for measurement of TGF‐β1 mRNA expression levels. We also assessed the plasma TGF‐β1 levels of cases (n = 88) and healthy subjects (n = 120). Results The TGF‐β1 producer genotype, −509TT, was not associated with an increased risk of colorectal cancer compared with other genotypes. Colorectal cancer patients especially those with a more aggressive disease behaviour were more frequently associated with C allele. Conclusion The results suggest that TGF‐β1 −509C>T polymorphism is not associated with either an increased risk or progression of colorectal cancer.     

Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder

What's known on the subject? and What does the study add? Steroid hormone receptor signals have been implicated in bladder tumourigenesis and tumour progression. The expression of androgen and/or oestrogen receptors has been assessed in bladder cancer, leading to conflicting data of expression levels and their relationship to histopathological characteristics of the tumours. We simultaneously analyze three receptors in non‐neoplastic bladder tissues as well as in primary and metastatic bladder tumour specimens. Our data demonstrate that the expression status correlates with tumour grades/stages and patients’ outcomes.

OBJECTIVE

• ? To assess the expression of the androgen receptor (AR) and oestrogen receptors (ERs) in bladder tumours because recent studies have shown conflicting results and the prognostic significance of their expression remains unclear.

PATIENTS AND METHODS

• ? We investigated the expression of AR, ERα and ERβ in 188 bladder tumour specimens, as well as matched 141 non‐neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry.
• ? We then evaluated the relationships between their expression and the clinicopathological features available for the present patient cohort.

RESULTS

• ? AR/ERα/ERβ was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumours and 71%/64%/71% of metastatic tumours.
• ? Significantly lower expression of AR/ERα was found in high‐grade tumours (36%/23%) and tumours invading muscularis propria (33%/19%) compared to low‐grade tumours (55%; P= 0.0232/38%; P= 0.0483) and tumours not invading muscularis propria (51%; P= 0.0181/35%; P= 0.0139), respectively.
• ? Significantly higher expression of ERβ was found in high‐grade tumours (58%) and tumours invading muscularis propria (67%) compared to low‐grade tumours (29%; P= 0.0002) and tumours not invading muscularis propria (34%; P < 0.0001), respectively.
• ? Kaplan–Meier and log‐rank tests further showed that positivity of ERβ (but not AR or ERα) was associated with the recurrence of low‐grade tumours (P= 0.0072); the progression of low‐grade tumours (P= 0.0005), high‐grade tumours not invading muscularis propria (P= 0.0020) and tumours invading muscularis propria (P= 0.0010); or disease‐specific mortality in patients with tumours invading muscularis propria (P= 0.0073).

CONCLUSIONS

• ? Compared to benign bladders, a significant decrease in the expression of AR, ERα or ERβ in bladder cancer was seen.
• ? Loss of AR or ERα was strongly associated with higher grade/more invasive tumours, whereas ERβ expression was increased in high‐grade/invasive tumours and predicted a worse prognosis.

     

Timing and detection of metachronous colorectal cancer

Background: Surveillance following surgery for colorectal cancer aims to detect treatable disease relapse or metachronous neoplasia. Metachronous cancers have been reported within a short duration of follow‐up, and may be due to missed lesions, seeding into polypectomy wounds or accelerated tumorigenesis related to genetic instability. The purpose of this study was to establish the timing and method of detection of metachronous cancers in a large population of patients in a surveillance database. Methods: This retrospective clinical study used patients with an elevated risk of colorectal neoplasia included in a colonoscopy‐based surveillance programme to identify those with two or more colorectal cancers, as well as the timing and method of detection of the tumours. Colonoscopy reports and histopathology results were reviewed to determine quality of bowel preparation, tumour location, and polypectomy data. Results: Fourteen (2.5%) of 569 patients with colorectal cancer developed metachronous malignant tumours, nearly half of which were identified within 3 years of follow‐up by surveillance colonoscopy or an interval faecal immunochemical test for globin. None of these had a previous polypectomy at the site of the second tumour, bowel preparation at the original colonoscopy was good in most cases, and no metachronous tumour occurred at a colonic flexure. Conclusion: Metachronous cancers can occur early during follow‐up after curative intent resection, and early colonoscopic surveillance may be warranted.     

Short‐term and long‐term outcomes of patients with malignant large bowel obstruction

Objective: The aim of the present study was to review our experience in the surgical management of patients with obstructing colorectal cancers over an 11‐year period, 1987–1997. Patients and methods: Retrospective review of case records of 275 patients (male: 177; female 98) who had undergone emergency surgery for obstructing colorectal cancers was performed. Tumours proximal to splenic flexure were defined as proximal tumours while those at or below the splenic flexure were defined as distal tumours. Results: The obstruction was caused by proximal tumours in 88 (32%) patients. The resection rate and the primary anastomotic rate were higher for proximal tumours compared with distal tumours (95.5%vs 85.6%, P = 0.014; 92%vs 30.5%, P < 0.001). For distal tumours, stoma rate was found to be influenced by the following factors: preoperative albumin level, duration of observation after admission, operating surgeons’ years of experience, bowel perforation and site of the obstructing tumour. Multivariate analysis disclosed that surgeons’ experience was the only independent factor predicting stoma formation. The in‐hospital mortality and the anastomotic leakage rates were 15.3% and 5.6%, respectively. Tumour stage was the only prognostic factor affecting the disease‐free survival after curative resection. The 5‐year disease‐free survival rates for Dukes’ B and C disease were 66% and 37.2%, respectively. Conclusions: Tumour stage was a significant prognostic factor for patients with obstructing colorectal cancers. Emergency surgery for distal tumours should preferentially be performed by more experienced surgeons in order to achieve a higher anastomotic rate.     

Impact of the bowel‐screening programme on the diagnosis of colorectal cancer in Ayrshire and Arran

Aim Bowel screening aims to reduce colorectal‐cancer mortality by the detection and treatment of early‐stage asymptomatic disease and the removal of precancerous adenomas. Bowel screening started in Ayrshire and Arran in September 2007. We report the impact of this screening on the diagnosis and stage of colorectal cancer and characterize screen‐detected cancers in comparison with those diagnosed through other pathways. Method Diagnoses were identified from an audit database. Referrals were grouped into screen detected, routine, urgent and emergency presentations. Results Between January 2001 and December 2010, 2289 diagnoses of colorectal cancer were made. From 2001 to 2006, the mean (range) number of new colorectal‐cancer diagnoses per year was 210 (198–220). Between 2007 and 2010, the mean (range) number of diagnoses per year was 256 (239–274), a significant (P = 0.008) increase. Since September 2007, 877 colorectal cancers have been diagnosed: 17% were screen detected; 11% were detected as a result of routine GP referral; 51% were detected after urgent GP referral; and 21% were emergency presentations. TNM stage increased with urgency of referral. Approximately two‐thirds (66%) of screen‐detected colorectal cancers were node negative vs 25% of emergency presentations (P < 0.001). Most screen‐detected cancers were distal to the splenic flexure (75%). Screened cancers had favourable pathology; lower T and N stages (both P < 0.001), less venous invasion (P < 0.001) and better differentiation (P < 0.05). Similar results were seen after stratification for TNM stage. Screening has not yet resulted in a significant shift towards early‐stage disease since 2007. Conclusion Screening has been associated with an increase in the numbers of both new and early‐stage colorectal cancers. Screen‐detected cancers are predominantly early‐stage disease with favourable pathology. At present, it remains to be seen whether screening will ultimately translate into an overall reduction in advanced‐stage disease.     

Hereditary mixed polyposis syndrome due to a BMPR1A mutation

The conditions Juvenile Polyposis Syndrome (JPS) and Hereditary Mixed Polyposis Syndrome (HMPS) are associated with an increased risk of colorectal carcinoma. The genetic mechanisms which explain these conditions have until recently been poorly understood. Recent interest has focused on the transforming growth factor (TGF)‐β signalling pathway and, in particular, on mutations in the SMAD4 gene. However, not all cases of JPS and HMPS have mutations in SMAD4 and focus has now shifted to other components of the TGF‐β pathway to clarify the genetic mechanisms involved in these conditions. In this report, we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family.     

Reduction in Peyronie's‐like plaque size using a vacuum erection device in a rat model of Peyronie's disease via the TGF‐β/SMAD signalling pathway

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea (TA). This study aimed to determine the therapeutic effects of a vacuum erection device (VED) in an animal model of PD and explore the possible mechanisms. Twenty‐seven male Sprague‐Dawley rats were used. The sham group (group A) (N = 9) received a 50‐μl‐saline vehicle injection into the TA, while the remaining 18 rats (groups B and C) received a TGF‐β1 injection into the TA. The treatment group (group C) underwent VED therapy for 10 days after the TGF‐β1 injection. Erectile function was then assessed at day 42. Rats injected with TGF‐β1 showed significantly lower intracavernous pressures than those in the sham group (p < 0.0001). After VED therapy, erectile function was significantly better in the treatment group than in the PD group (group B) (p < 0.0147). Masson's trichrome staining confirmed Peyronie's‐like plaques at the TGF‐β1 injection site in the PD group. Furthermore, the treatment group showed markedly smaller fibrotic plaque sizes than the PD group. A significant increase in TGF‐β1, SMAD2, SMAD3 and p‐SMAD2/3 protein expression was observed 6 weeks after the TGF‐β1 injection. However, the expression of the same proteins decreased after VED therapy. Protein expression trends were confirmed using immunohistochemistry analysis. The findings of this study demonstrate that VED therapy can reduce Peyronie's‐like plaque size in a rat model of PD while simultaneously improving erectile function.     

The relationship between serum vascular endothelial growth factor A and microsatellite instability in colorectal cancer

Aim It has been suggested that colorectal neoplasms with or without microsatellite instability (MSI) can stimulate angiogenesis in different ways. The vascular endothelial growth factor (VEGF) system is essential for the angiogenetic process and the growth of malignant tumours. The aim of this study was to analyse the relationship between serum VEGF‐A and the MSI status of patients with colorectal cancer (CRC). Method In the study, 249 patients with CRC were divided into a test cohort of 83 patients and a validation cohort of 166. MSI was determined using immunohistochemistry. Tumours lacking protein expression of any of the four mismatch repair genes (MLH1, PMS2, MSH2 or MSH6) were labelled as high MSI. The rest were considered to be microsatellite stable (MSS). The serum VEGF‐A analyses were performed by ELISA. Results The tumours of 15 patients in the test cohort and 27 in the validation cohort were classified as MSI. In the test cohort, patients with an MSI tumour had a significantly higher median serum VEGF‐A concentration [617 pg/ml (95% CI 445–863)], compared with patients with an MSS tumour, [317 pg/ml (95% CI 224–386)], P = 0.01. A similar relationship was confirmed in the validation cohort, P = 0.04. Conclusion This study provides some evidence to suggest that patients with an MSI tumour have higher serum VEGF‐A levels than patients with an MSS tumour. If further validated, these findings could be of importance when considering the effects of anti‐VEGF‐A treatment.     

Screen‐detected colorectal cancers show improved cancer‐specific survival when compared with cancers diagnosed via the 2‐week suspected colorectal cancer referral guidelines

Aim Biennial screening for colorectal cancer using faecal occult blood testing has been shown to reduce the relative risk of mortality from colorectal cancer. The Norwich screening centre commenced screening in July 2006 and so far has diagnosed over 350 patients with colorectal cancer. We compared the stage at diagnosis and cancer‐specific mortality and survival in patients diagnosed through screening with a cohort of symptomatic patients with colorectal cancer within the same age range. Method A comparative analysis was undertaken of all screen‐detected colorectal cancer patients diagnosed between July 2006 and December 2010, with an age‐matched group of patients diagnosed in the Norfolk and Norwich Hospital through the 2‐week suspected colorectal cancer guidelines. Results Three hundred and fifty‐six cases of colorectal cancer were diagnosed through the screening programme, in patients with an age range of 60–79 years. In the same time period, 292 patients in the same age range were diagnosed with colorectal cancer through the 2‐week suspected colorectal cancer pathway. Sixteen patients in the screening group had evidence of metastatic disease at presentation compared with 62 in the symptomatic group (χ², P < 0.001). The proportion of T1/T2 and Dukes A cancers was significantly greater in the screening group (χ², P < 0.001). There were 21 colorectal cancer‐related deaths in the screening group compared with 66 in the symptomatic group. Survival analysis curves showed significantly better survival in the screening group (log‐rank analysis P < 0.001). Conclusion Screening for colorectal cancer identifies cancers at a significantly earlier stage than in symptomatic patients, with subsequent improvement in cancer‐specific survival.     

Phenotypic characteristics of hereditary non-polyposis colorectal cancer by the Amsterdam criteria: an Asian perspective

Background: Hereditary non‐polyposis colorectal cancer (HNPCC) is an autosomal disease with a 68–82% lifetime risk of colorectal cancer (CRC). This study examined the phenotypic characteristics of CRC in Amsterdam criteria‐positive Asian patients from the Singapore Polyposis Registry. Methods: Hereditary non‐polyposis CRC patients, defined by the Amsterdam I and II criteria, prospectively monitored in the Singapore Polyposis Registry over a 16‐year period were reviewed. Clinical data were obtained from a computerized database and parameters, such as age of diagnosis, type and location of CRC, other associated cancers in the pedigree, cancer recurrence and survival were analysed. Results: Fifty‐two patients (31 men and 21 women) from 42 unrelated families, with a median age of 44.5 years (range 27–73 years), fulfilled either Amsterdam I or II criteria and were included in our analysis. The racial distribution was 91% (n = 47) Chinese and 9% (n = 5) Malays, with a median follow up of 44.9 months (range 2–183 months). Significantly, 69% of tumours in this Amsterdam‐defined cohort were left sided, with most being sigmoid cancers. Sixty per cent of all the tumours presented at a late stage (Dukes’ C or D). Left‐sided tumours presented with more advanced Dukes’ stage (P = 0.096) and a higher rate of metastatic disease (P = 0.08) compared with right‐sided lesions. There were, however, no significant differences in either disease‐free or overall survival between right‐sided and left‐sided tumours. Conclusion: This study emphasized the significant left‐sided predominance of CRC in Amsterdam I and II‐defined patients from our predominantly Chinese population, in contrast to those classically described in Lynch syndrome. Amsterdam criteria thus may not be suitable for diagnosing HNPCC in Asian populations and a greater emphasis should be made towards routine molecular diagnosis of mismatch repair gene defects in suspected HNPCC patients of Asian decent.     

The survival effect of E‐cadherin and catenins in colorectal carcinomas

Aim The E‐cadherin/catenin complex plays an important role in epithelial tissue architecture. Decreased expression of cell adhesion molecules (E‐cadherin, α‐, β‐ and γ‐catenin) have been reported to correlate with invasive behaviour. The aim of this study was to investigate the relation between the expression of adhesion molecules and clinicopathological characteristics and survival in colorectal carcinoma. Method The expression of adhesion molecules were studied by immunohistochemistry in 138 colorectal carcinomas. Results The mean age of the patients was 65 years (range: 21–89 years). In primary carcinomas, a reduction in membranous expression of E‐cadherin, α‐catenin, β‐catenin, γ‐catenin was demonstrated (70%, 68%, 73%, 77%, respectively). Nuclear expression of β‐catenin was found in eight (5%) patients. Decreased membranous β‐ and γ‐catenin expression significantly correlated with tumour differentiation (P = 0.013, P = 0.03, respectively). There was a significant association between advanced stage of the tumour and decreased membranous α‐catenin expression (P = 0.012). Decreased E‐cadherin and β‐catenin membranous expression correlated with short survival following curative resection of the primary tumour (P = 0.04, P = 0.03, respectively). Conclusion The decreased membranous expression of E‐cadherin and β‐catenin and increased cytoplasmic expression of β‐catenin might be used as a prognostic marker to monitor patients with colorectal cancer.     

Colorectal cancer in the young: a 12-year review of patients 30 years or less

Objectives As the incidence of young colorectal cancer is rising, a review of the characteristics of such malignancy in those under 30 years of age is timely at this stage. Patients and methods Thirty‐nine patients (21 M, 18 F) were operated upon over a 12‐year period in a single centre. The mean age was 25 years and median follow‐up was 20 months. Results Rectal bleeding, change in bowel habit and abdominal pain were the commonest symptoms. Six patients had a positive family history, while four others were diagnosed as index cases of familial adenomatous polyposis. Rectal tumours made up 43% of all colorectal cancers diagnosed. Seventy percent of patients presented at an advanced stage, but curative resection was attempted for 29 patients. Eight underwent palliative resections, 1 had an ileostomy while another underwent a bypass procedure. Eleven patients have died, 14 had no evidence of recurrent disease while 3 were still alive with recurrent disease. Conclusion Age does not affect survival, and early endoscopy is recommended for all with persistent symptoms. Early diagnosis, radical resection and adjuvant therapy still form the cornerstone in management of colorectal cancer in this age group.