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S S Cross

Publications and source records attributed to S S Cross.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review.

BACKGROUND: Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. METHODS: Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. RESULTS: None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. CONCLUSION: Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity.

Aged↗
PubMed2006

Lactate dehydrogenase-B is silenced by promoter hypermethylation in human prostate cancer.

In order to identify novel candidates associated with prostate cancer metastasis, we compared the proteomic profile of the poorly metastatic human prostate cancer cell line LNCaP, with its highly metastatic variant LNCaP-LN3, by two-dimensional gel electrophoresis. A major protein spot (pI of 5.9 and molecular weight of 37 kDa) was seen in LNCaP cells, but not in LNCaP-LN3 cells and was identified as lactate dehydrogenase-B (LDHB), by tandem mass spectrometry. Furthermore, enzyme kinetic assays and zymography showed a higher LDH enzyme activity in LNCaP cells compared with LNCaP-LN3. Bisulphite-modified DNA sequencing showed promoter hypermethylation in LNCaP-LN3 cells but not in LNCaP, Du145, PC3, CWR22 or BPH45 cells. Treatment of LNCaP-LN3 cells with 5'-azacytidine caused re-expression of LDHB transcripts. In tissues, LDHB promoter hypermethylation occurred at a higher frequency in prostate cancer, 14/ 31 (45%), compared to adjacent nonmalignant or benign tissue, 2/19 (11%) (P < 0.025). Immunohistochemistry showed a higher frequency of LDHB expression in benign or non-malignant tissues, 59/ 73 (81%), compared to cancer cases, 3/53 (6%) (P < 0.001). Absent LDHB expression was also seen in 7/7 (100%) cases of metastatic cancer in bone. Our data are the first to show loss of LDHB expression in prostate cancer, the mechanism of which appears to involve promoter hypermethylation.

Amino Acid Sequence↗
PubMed2006

Methylational urinalysis: a prospective study of bladder cancer patients and age stratified benign controls.

Tumour suppressor gene (TSG) methylation has been proposed as a diagnostic marker for urothelial cancer (UC). Here, we compare the frequency of urinary TSG methylation in young and elderly patients, with and without UC. Urine samples were obtained prospectively from 35 UC patients, 35 benign controls over the age of 70 years and 34 healthy volunteers under the age of 40 years. Methylation analysis was performed for eight gene promoters using quantitative methylation-specific PCR. Methylation was detected in urine DNA from all three patient groups. The highest frequencies were seen in UC patients. Significantly less methylation was present in control samples than UC cases for RASSF1a and APC (P < 0.034). The 'methylation index' and level of methylation was highest in the UC group and lowest in the young control group. A marker panel of RASSF1a, E-cad and APC generated a sensitivity of 69%, a specificity of 60% and a diagnostic accuracy of 86%. TSG methylation is detectable in urine DNA from patients with and without bladder cancer. The frequency and extent of methylation appears to increase with age and malignancy. The lack of tumour specificity suggests that further investigation is required before this test is introduced into clinical practice.

Adult↗
PubMed2006

Expression of receptor activator of nuclear factor kappabeta ligand (RANKL) and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) in breast cancer, and their relations with osteoprotegerin, oestrogen receptor, and clinicopathological variables.

BACKGROUND: Receptor activator of nuclear factor kappabeta ligand (RANKL) has an important role in bone remodelling, and tumour necrosis factor related, apoptosis inducing ligand (TRAIL) can induce apoptosis in cancer cells. Their functions are linked by their interactions with osteoprotegerin (OPG). OBJECTIVE: To investigate the expression of RANKL and TRAIL in a large series of unselected breast cancers and to analyse the relations between these expressions and the expression of OPG, oestrogen receptor, and clinicopathological variables. METHODS: 395 breast cancers were sampled into tissue microarrays and immunohistochemistry undertaken for RANKL and TRAIL. RESULTS: There was strong expression of RANKL in 14% of the cancers and strong expression of TRAIL in 30%. Expression of RANKL had a negative association with expression of oestrogen receptor (p = 0.036). Expression of TRAIL had a negative association with the Nottingham Prognostic Index (p = 0.021). There was a significant negative relation between expression of RANKL and TRAIL (p<0.005). Unsupervised cluster analysis produced a dendrogram that showed a clear division into two groups, and the expression of oestrogen receptor was significantly higher in one of those groups (p = 0.012). CONCLUSIONS: There is apparent loss of expression of RANKL in 86% of breast cancers; those tumours that retain expression tend to be oestrogen receptor negative and of a high histological grade. There is strong expression of TRAIL in 30% of breast cancers and these tend to be of better prognostic type. These results may be important in the processes of metastasis to bone and the apoptotic cell death pathway in cancer.

Apoptosis Regulatory Proteins↗
PubMed2006

Evidence for the early onset of aberrant promoter methylation in urothelial carcinoma.

There is evidence that carcinoma in situ (CIS) is the precursor of invasive urothelial carcinoma, a tumour characterized by frequent gene promoter methylation. The timing of altered DNA methylation is unknown in this pathway. Here we investigate gene methylation in 196 consecutive samples of normal urothelium, CIS, and tumours from 104 patients with both CIS and invasive urothelial carcinoma using quantitative methyl-sensitive polymerase chain reaction for six genes (p16, p14, E-cadherin, RARbeta2, RASSF1a, and GSTP1). Control normal urothelial samples from 15 patients with no history of urothelial carcinoma were also analysed. Immunohistochemistry established the expression of well-characterized CIS markers p53 and cytokeratin 20. Promoter methylation occurred frequently in both normal urothelium and CIS samples from patients with urothelial carcinoma, and increased with progression from normal to invasive urothelial carcinoma, at both specific loci (chi2 test: E-cadherin, p=0.0001; RASSF1a, p=0.003, RARbeta2, p=0.007, p16, p=0.024) and in general (methylation indices [t-test, p<0.0001]). Methylation was associated with cytokeratin 20 expression (t-test, p=0.004) and poor prognosis, and with increased progression to tumour death in patients whose CIS samples showed methylation, in comparison with those without methylation (log rank p<0.03). Promoter methylation occurs early in the urothelial carcinogenic pathway and appears to be a good biomarker of the invasive urothelial carcinoma phenotype.

Adult↗
PubMed2006

High-magnification chromoscopic colonoscopy in ulcerative colitis: a valid tool for in vivo optical biopsy and assessment of disease extent.

BACKGROUND AND STUDY AIMS: Colonoscopy with mucosal biopsy is currently considered to be the "gold standard" investigation for the evaluation of disease activity and disease extent in ulcerative colitis. Conventional colonoscopic criteria are inadequate for assessing disease extent and for predicting clinical relapse, however. Histopathological markers of relapse, such as microscopic crypt abscess formation and mucin depletion cannot be identified using conventional endoscopy. The aim of this study was to evaluate the efficacy of high-magnification chromoscopic colonoscopy for the in vivo assessment of histopathological inflammation and disease extent using standardised endoscopic and histopathological criteria. PATIENTS AND METHODS: Total colonoscopy using the Olympus CF240Z magnifying colonoscope was performed prospectively in 325 consecutive patients with a known diagnosis of ulcerative colitis. A "biphasic" examination of all five colonic segments and the rectum was performed with conventional endoscopy followed by magnification imaging and biopsy. Disease activity was documented using Baron's classification, modified Saitoh criteria for magnification imaging, and Matts' histopathological grading. RESULTS: A total of 1800 images from 300 patients were analyzed (25 patients were excluded). The kappa coefficients of agreement between Saitoh's magnification criteria grades 1/2, 3/4, and 5/6 and Matts' histopathological grades 1/2, 3a/b, and 4/5 were 0.96, 0.62, and 0.51, respectively. Mild, moderate, and severe histopathological disease (Matts' grades 1/2, 3a - 4, and 5) were represented more accurately using Saitoh's criteria than by conventional Baron scores for all clinical parameters ( R = 0.976; P < 0.001). Magnification imaging was significantly better than conventional colonoscopy for predicting disease extent in vivo ( P < 0.0001). CONCLUSIONS: This is the largest prospective study and the only Western group to report on this application of magnification imaging. High-magnification imaging provides a sensitive and specific in vivo "virtual biopsy" in ulcerative colitis and so an instant biomarker for disease relapse, while accurately predicting disease extent. High-accuracy optical biopsy can limit the number of biopsies required, with significant cost savings for pathology services.

Adolescent↗
PubMed2006

"Salvage" endoscopic mucosal resection in the colon using a retroflexion gastroscope dissection technique: a prospective analysis.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection and submucosal dissection can provide curative endoscopic therapy for Paris type I/II adenomas and node-negative early cancer. No studies have addressed the technical feasibility of retroflexion endoscopic dissection methods for luminal "salvage" therapy in patients considered unresectable using conventional forward-viewing resection. PATIENTS AND METHODS: Colonoscopy using an Olympus GIF-XQ240 gastroscope was carried out in 76 patients with Paris type I/II adenomas, early colorectal cancer (CRC), or laterally spreading tumors (LSTs) when the index endoscopist considered the lesion to be unresectable due to retrograde fold involvement. Endoscopic mucosal resection (EMR) and submucosal dissection were carried out using a complete retroflexion technique. Endoscopic and miniprobe 20-MHz or 12.5-MHz ultrasound follow-up data were collected prospectively up to 24 months after the index resection. RESULTS: Cecal intubation or cannulation to the neoterminal ileum was achieved in 76 (100 %) cases. Forty lesions (53 %) were classified in accordance with the Paris criteria as Is; 16 (21 %) as type II; 10 (13.5 %) as LST-G; and 10 (13.5 %) as LST-NG. Eight lesions (10 %) were excluded from EMR on the basis of endoscopic ultrasound criteria, with 68 of the 76 lesions (89 %) meeting the criteria for endoluminal resection. The median intubation time was 16 min (range 3-32 min). The median resection times were 98 min (range 30 - 242 min), 36 min (range 10-60 min), 172 min (range 20 - 240 min), and 60 min (range 10-116 min) for Paris Is, II, LST-G, and LST-NG lesions, respectively. LST-G morphology was associated with a high median submucosal injection volume in comparison with all other Paris types ( P < 0.05) and with a prolonged resection time ( P < 0.01). Sixty-one patients (94 %) completed the surveillance protocol. Higaki recurrence criteria were met in seven patients (11 %), with six undergoing successful adjunctive endoluminal resection. After 24 months of follow-up, the "cure" rate with endoscopic resection was 60 out of 61 (98 %). CONCLUSIONS: This is the first prospective study to address the safety and medium-term efficacy of retroflexion endoscopic resection in the colon. When appropriate exclusion criteria are applied, selected patients can receive curative resection using the retroflexion technique. "Salvage" endoluminal therapy may therefore be possible in such cases when surgical resection would otherwise have been required.

Adenoma↗
PubMed2006

Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor kappaB ligand (RANKL) in human breast tumours.

BACKGROUND: Osteoprotegerin (OPG) is involved in the regulation of bone turnover through binding to the receptor activator of nuclear factor kappaB ligand (RANKL), and has also been reported to be a potential survival factor for several different cell types. The survival effects are mediated through inhibition of the activity of tumour necrosis factor related apoptosis inducing ligand (TRAIL). Both breast and prostate cancer cells produce sufficient amounts of OPG to be protected against the effects of TRAIL in vitro. AIMS: To investigate the spatial expression of OPG, RANKL, and TRAIL in non-neoplastic breast tissue and breast cancer, and its relation with oestrogen receptor (ER) expression. METHODS: Forty breast cancers (20 ER+, 20 ER-) and five non-neoplastic breast tissue samples were stained with antibodies against OPG, RANKL, and TRAIL. RESULTS: OPG was not expressed in non-neoplastic breast tissue except when colocalised with altered columnar epithelium. RANKL was expressed at the apical surface of luminal epithelial cells and TRAIL was expressed in myoepithelial cells. All three proteins were expressed in some breast cancers but showed no significant association with tumour type. OPG expression showed a significant positive correlation with ER expression (p = 0.011). CONCLUSIONS: This is the first published study of the spatial expression of OPG, RANKL, and TRAIL in breast tissue and breast cancer. The localisation of each protein was specific and they were not colocalised. This specificity may provide a useful marker of functional differentiation in breast cancer; for example, TRAIL expression as a marker of myoepithelial differentiation.

Apoptosis Regulatory Proteins↗
PubMed2005

High magnification chromoscopic colonoscopy or high frequency 20 MHz mini probe endoscopic ultrasound staging for early colorectal neoplasia: a comparative prospective analysis.

BACKGROUND: Successful endoscopic management of early colorectal cancer using endoscopic mucosal resection requires the mandatory prediction of invasive depth and lymph node metastasis. Previous data using the Nagata crypt types Vn(B)/(C) as clinical indicators of T2/N+ disease have shown low specificity (50%) with a tendency to over stage lesions. New mini probe ultrasound "through the scope" imaging permits staging of lesions proximal to the rectum using direct endoscopic visualisation. AIM: To compare the staging accuracy of the Nagata crypt type V with mini probe high frequency 20 MHz endoscopic ultrasound. METHODS: Sixty two patients with a Paris type II flat cancer were imaged using magnification colonoscopy followed by 20/12.5 MHz ultrasound in a "back to back" design. Crystal violet staining (0.05%) at 100x magnification permitted Nagata crypt criteria to be defined. Submucosal deep invasion (sm3+) was defined at ultrasound by the presence or absence of a disrupted third sonographic layer. Predicted T0/1:N0 lesions were resected using endoscopic mucosal resection with the remaining referred for surgery. Ultrasound and magnification staging were then compared with the resected histopathological specimens. RESULTS: One patient was excluded from the study due to poor bowel preparation. Fifty two lesions from 52 patients therefore met inclusion criteria (12 sm1/13 sm2/27 sm3+). Ultrasound (20 MHz) was significantly more accurate for invasive depth staging compared with Nagata stage (p<0.0001) (overall accuracy 93% and 59%, respectively). The sensitivity for lymph node metastasis detection using ultrasound and magnification was 80% and 31%, respectively (p<0.001). The negative predictive value of ultrasound for invasive depth was better than that observed using magnification (88%/47%, respectively). The prevalence of nodal disease overall was 19% (10/52), with 80% (8/10) node positive lesions occurring in the sm3+ lesion group. CONCLUSIONS: High frequency 20 MHz ultrasound is superior to magnification alone when differentiating T1/2 disease with a high positive predictive value for sm3 differentiation. Sm3+ invasion was associated with nodal metastasis.

Adult↗
PubMed2005

Endoscopic ultrasound miniprobe staging of colorectal cancer: can management be modified?

BACKGROUND AND STUDY AIMS: Miniprobe ultrasound technology allows in-vivo luminal staging of colorectal cancer with a probe that passes directly through the colonoscope's instrument port. Conventional rigid radial echoscopes are limited by the need for a second examination, an inability to image stenotic lesions, and the inaccessibility of proximal tumours. Since minimally invasive resection techniques are now possible, a sensitive preoperative staging tool is needed to optimize patient selection. The aim of this study was to examine the accuracy of miniprobe ultrasound imaging in the preoperative staging of colorectal cancer and to examine the value of the technique for management decisions. PATIENTS AND METHODS: In a prospective study, a total of 131 consecutive patients with adenocarcinoma or broad-based polyps of the colorectum underwent 12.5-MHz miniprobe ultrasonography examinations conducted by a single endoscopist. Staging criteria for depth of tumour infiltration and nodal status were determined. Nodal disease was defined as the presence of a hypoechoic, round, defined boundary lesion larger than 10 mm in diameter. T0-T1N0 lesions were resected using endoscopic mucosal resection, and patients with lesions staged as T2N1 were referred for surgical resection. Tumour staging using endoscopic ultrasonography was then compared with the histopathological specimens. RESULTS: The accuracy of T staging using endoscopic ultrasonography was 96 % in comparison with the histopathological specimen. Five lesions (4 %) were incorrectly overstaged as T3 - pathology stage T2. Understaging occurred in three lesions (endoscopic ultrasound stage T3 - pathology stage T4). The overall accuracy of nodal staging using endoscopic ultrasonography was 87 % (sensitivity 0.95, specificity 0.71, positive predictive value 0.87, negative predictive value 0.88). CONCLUSIONS: Miniprobe ultrasonography has a high overall accuracy for both T staging and N staging of colorectal cancer and may have an important role in selecting patients suitable for minimally invasive resection techniques.

Adult↗
PubMed2005

Indigo carmine-assisted high-magnification chromoscopic colonoscopy for the detection and characterisation of intraepithelial neoplasia in ulcerative colitis: a prospective evaluation.

BACKGROUND AND STUDY AIMS: Recent data suggest that panchromoscopy using methylene blue can improve the detection of intraepithelial neoplastic lesions in the context of surveillance colonoscopy for patients with chronic ulcerative colitis. This method has also been shown to provide a more accurate diagnosis of the extent of disease and inflammatory activity. Interval cancers are known to occur in patients with chronic ulcerative colitis despite the adoption of currently accepted surveillance biopsy protocols. We hypothesised that targeted chromoscopy alone, with high-magnification imaging, may increase the total number of intraepithelial neoplastic lesions detected, compared with conventional colonoscopy and biopsy surveillance according to current protocols. PATIENTS AND METHODS: A total of 350 patients with long-standing ulcerative colitis (>or=8 years) underwent surveillance colonoscopy using high-magnification chromoscopic colonoscopy (HMCC). Quadrantic biopsies at 10-cm intervals were taken on extubation in addition to targeted biopsies of abnormal mucosal areas. Defined lesions were further evaluated using modified Kudo crypt pattern analysis. These data were compared with data from 350 disease duration- and disease extent-matched control patients who had undergone conventional colonoscopic surveillance between January 2001 and April 2005. RESULTS: Significantly more intraepithelial neoplastic lesions were detected in the magnification chromoscopy group compared with controls (69 vs. 24, P<0.0001). Intraepithelial neoplasia was observed in 67 lesions, of which 53 (79%) were detected using magnification chromoscopy alone. Chromoscopy increased the number of flat lesions with intraepithelial neoplasia detected compared with controls (P<0.001). Twenty intraepithelial neoplastic lesions were detected from 12,850 non-targeted biopsies in the HMCC group (0.16%), while 49 intraepithelial neoplastic lesions were detected from the 644 targeted biopsies in the HMCC group (8%). From 12,482 non-targeted biopsies taken in the control group patients, 18 (0.14%) showed intraepithelial neoplasia. The yield of intraepithelial neoplastic lesions from targeted biopsies in the control group (i. e. without HMCC imaging), however, was only modestly improved at 1.6% (6/369). Using modified Kudo criteria, the sensitivity and specificity for differentiating neoplastic from non-neoplastic lesions using HMCC were 93% and 88% respectively. The total procedure time was significantly longer in the HMCC group compared with controls (P<0.02). CONCLUSIONS: Magnification chromoscopy improves the detection of intraepithelial neoplasia in the endoscopic screening of patients with chronic ulcerative colitis. Neoplastic and non-neoplastic mucosal change can be predicted with a high overall accuracy using magnification techniques. These adjunctive endoscopic techniques have important clinical implications and may lead to changes in current practice guidelines.

Biopsy, Needle↗
PubMed2005

Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers.

AIMS: To survey the expression of members of the S100 family of calcium-binding proteins in normal human tissues and common cancers using tissue microarrays. S100A6, S100A8, S100A9 and S100A11 have all been suggested to have potential roles in carcinogenesis and tumour progression but their expression has not been described in a wide range of human tissues and tumours. METHODS AND RESULTS: A custom-made tissue array, containing 291 tissue cores representing 28 tissue types and 21 tumour types, was used to produce sections that were immunostained for S100A2, S100A6, S100A8, S100A9, S100A11, calbindin 1, calbindin 2, S100B and parvalbumin. S100A6, S100A8 and S100A9 were expressed in 32%, 12% and 28% of breast cancers, respectively. There was a translocation of S100A11 expression from exclusively nuclear in normal tissues to cytoplasmic and nuclear in all common cancers. CONCLUSIONS: S100A6, S100A8, S100A9 and S100A11 are all expressed in common cancers, especially breast cancer. In addition, S100A11 undergoes a nucleocytoplasmic translocation which may have a direct influence on the proliferation of the cancer cells.

Calbindin 1↗
PubMed2005

A prospective analysis of extended endoscopic mucosal resection for large rectal villous adenomas: an alternative technique to transanal endoscopic microsurgery.

INTRODUCTION: Endoscopic mucosal resection is a safe resection tool for selected flat, sessile and lateral spreading tumours of the colon. Transanal microsurgical resection of select rectal neoplastic lesions is another accepted modality. Recent data suggests transanal microsurgery may have high complication rates. We conducted a prospective clinicopathological evaluation of an extended endoscopic mucosal resection technique for highly selected lesions of the rectum and assessed outcome data over a maximal 24-month period. PATIENTS AND METHODS: Eighty-three patients with known rectal neoplastic lesions underwent chromoscopic colonoscopy and on-table staging using a high-frequency (12.5 MHz) mini-probe EUS by a single endoscopist. Patients with T2 or node positive disease were referred for surgery. Following extended endoscopic mucosal resection patients were followed-up at 3, 6, 12 and 24 months post 'index' resection with chromoscopic endoscopy and EUS. Procedural complications, recurrence rates and outcome data were collected. RESULTS: Sixty-two patients fulfilled inclusion criteria. Median procedure time was 48 mins (range 32-126). Lateral spreading tumours (median diameter 30 mm; range 18-42 mm) and sessile lesions (median diameter 38 mm; range 25-86 mm) accounted for 19% and 81% of lesions, respectively. Ninety-seven percent of patients undergoing EMR were discharged within 6-h of procedure. Thirty-day re-admission and death rate was 0%. Bleeding complications occurred in 5/62 (8%) of patients with all achieving complete haemostasis using endo clips. None required transfusion. There were no procedural related complications or perforations. Overall 'cure' rate at a median follow-up of 16 months was 98%. CONCLUSIONS: Extended endoscopic mucosal resection for rectal neoplastic lesions can achieve superior results to those of per-anal excision and trans-anal microsurgery with regard to complications and recurrence rates. Extended endoscopic mucosal resection may be an alternative therapeutic modality in selected patients.

Adenoma, Villous↗
PubMed2005

The use of digital imaging, video conferencing, and telepathology in histopathology: a national survey.

AIMS: To undertake a large scale survey of histopathologists in the UK to determine the current infrastructure, training, and attitudes to digital pathology. METHODS: A postal questionnaire was sent to 500 consultant histopathologists randomly selected from the membership of the Royal College of Pathologists in the UK. RESULTS: There was a response rate of 47%. Sixty four per cent of respondents had a digital camera mounted on their microscope, but only 12% had any sort of telepathology equipment. Thirty per cent used digital images in electronic presentations at meetings at least once a year and only 24% had ever used telepathology in a diagnostic situation. Fifty nine per cent had received no training in digital imaging. Fifty eight per cent felt that the medicolegal implications of duty of care were a barrier to its use. A large proportion of pathologists (69%) were interested in using video conferencing for remote attendance at multidisciplinary team meetings. CONCLUSIONS: There is a reasonable level of equipment and communications infrastructure among histopathologists in the UK but a very low level of training. There is resistance to the use of telepathology in the diagnostic context but enthusiasm for the use of video conferencing in multidisciplinary team meetings.

Attitude of Health Personnel↗
PubMed2004

S100A6 (Calcyclin) is a prostate basal cell marker absent in prostate cancer and its precursors.

S100A6 (Calcyclin) is a calcium-binding protein that has been implicated in a variety of biological functions as well as tumorigenesis. The aim of our study was to investigate the involvement of S100A6 during prostate cancer development and progression. Using immunohistochemistry, the expression of S100A6 was examined in benign (n=66), premalignant (n=10), malignant (n=66) and metastatic prostate (n=5) tissues arranged in a tissue-microarray or whole sections as well as in prostate cancer cell lines. The S100A6 immunostaining pattern in tissues was compared with that of cytokeratin 5 (a basal cell marker) and 18 (a benign luminal cell marker). In all cases of benign epithelium, intense S100A6 expression was seen in the basal cell layer with absent staining in luminal cells. In all cases of prostatic adenocarcinoma (matched), metastatic lesions and 3/10 high-grade prostatic intraepithelial neoplasia lesions, an absence of S100A6 was seen. Western blotting and RT-PCR analysis of cell lines showed S100A6 expression to be absent in LNCaP, LNCaP-LN3 and LNCaP-Pro5 but present in Du145, PC3, PC-3M and PC-3M-LN4. LNCaP cells treated with 5-Azacytidine, caused re-expression of S100A6 mRNA. Sequencing of bisulphite modified DNA showed CpG methylation within the S100A6 promoter region and exon 1 of LNCaP, LNCaP-LN3 and LNCaP-Pro5 cell lines but not in Du145 cells. Our data suggest that loss of S100A6 protein expression is common in prostate cancer development and may occur at an early stage. The mechanism of loss of expression may involve hypermethylation of CpG sites. The finding of intense S100A6 expression in the basal cells of benign glands but loss of expression in cancer could be useful as a novel diagnostic marker for prostate cancer.

Adenocarcinoma↗
PubMed2004

High-magnification chromoscopic pouchoscopy: a novel in vivo technique for surveillance of the anal transition zone and columnar cuff following ileal pouch-anal anastomosis.

BACKGROUND: Persistence of underlying disease in the residual rectal mucosa and anal transition zone (ATZ) following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis and familial adenomatous polyposis provides a site for potential malignancy. For this reason endoscopic surveillance is performed, although conventional assessment may be unreliable. We hypothesized that the novel technique of high-magnification chromoscopic pouchoscopy (HMCP) may permit accurate anatomical localization of this high risk zone in vivo and permit improved biopsy accuracy. PATIENTS AND METHODS: We studied 132 patients with IPAA using HMCP. Three distinct zones were defined using magnification endoscopy: ATZ, appearing as a linear cellular marix; columnar cuff, identifiable by a type I crypt pattern; and ileal pouch body, appearing as villous projections. Quadrantic biopsies of these zones were taken in addition to biopsies of any other lesions noted. RESULTS: A total of 1586 biopsies were taken from zones 1-3 (median, 12; range, 5-16 per patient). Overall biopsy-targeting accuracies using magnification guidance as compared with histopathology were 82%, 73% and 91% for the ATZ, cuff and pouch body, respectively. No dysplasia was identified in the quadrantic surveillance biopsies. Histologically confirmed columnar metaplasia was visualized in vivo using magnification chromoscopy. Patients with IPAA >3 years' duration were more likely to have pouch reservoir columnar metaplasia as compared to those <3 years (p<0.01). Pouch reservoir metaplasia was associated with a pre-morbid diagnosis of high-grade dysplasia or carcinoma within the premorbid colectomy specimen (p<0.001). CONCLUSIONS: This is the first study to evaluate this novel application of high magnification chromoscopy. Magnification pouchoscopy is a valid predictor of ATZ and cuff anatomy, permitting accurate biopsy targeting. Further randomized studies validating this technique with an emphasis on dysplasia detection in larger cohorts are required.

Adult↗
PubMed2004

Proteomic analysis of voided urine after prostatic massage from patients with prostate cancer: a pilot study.

OBJECTIVES: Serum prostate-specific antigen measurements are widely used for the early detection of prostate cancer but lack specificity, thus warranting the search for additional biomarkers. METHODS: Two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis was used to investigate the protein profiles of voided urine after prostatic massage from 6 patients with histologically confirmed prostate cancer and 6 age-matched patients with benign prostatic hyperplasia. RESULTS: The median number of protein spots per gel was lower in the urine from the patients with cancer (median 143 spots, range 118 to 163) than in the urine from those with benign prostatic hyperplasia (median 154 spots, range 142 to 209), although the difference was not statistically significant. MALDI-TOF-MS analysis identified six commonly expressed proteins: alpha-enolase, isocitrate dehydrogenase, beta-2-microglobulin, alpha-1-microglobulin, complex-forming glycoprotein HC, and PRO2044. Of the five protein spots seen in a subset of patients with cancer, one was identified as calgranulin B/MRP-14. Immunohistochemical staining of prostatic tissue showed greater expression of calgranulin B/MRP-14 in 2 of 7 well-differentiated, 1 of 12 moderately differentiated, and 0 of 8 poorly differentiated tumors relative to adjacent benign tissue; expression of calgranulin A/MRP-8, a heterodermic binding partner of calgranulin B/MRP-14, was absent. CONCLUSIONS: The role of urinary calgranulin B/MRP-14 as a potential novel marker for prostate cancer needs additional investigation.

Aged↗