Immunohistochemical detection of cripto-1, amphiregulin and transforming growth-factor-alpha in human gastric carcinomas and intestinal metaplasias

The expression and localization of cripto-1 (CR-1), amphiregulin (AR) and transforming growth factor alpha (TGFalpha) were assessed by immunocytochemistry in 37 primary human gastric tumors, 30 noninvolved gastric mucosa samples that were adjacent to carcinoma but exhibited intestinal metaplasia and 37 adjacent, noninvolved gastric mucosa samples. Seventeen (46%), nineteen (51%) and twenty-one (57%) carcinomas showed staining for CR-1, AR and TGFalpha, respectively; whereas sixteen (53%), eight (26%) and five (17%) intestinal metaplasias were reactive with the anti-CR-1, anti-AR and anti-TGFalpha antibodies, respectively. In contrast, none of the normal, noninvolved gastric mucosa samples reacted with the TGFalpha antibody and only 1 (3%) of these samples showed weak staining with the anti-CR-1 antibody. However, 8 (21%) of the normal gastric mucosa samples showed moderate levels of staining with the AR antibody. Within the carcinomas, there was a slight trend for association between TGFalpha and CR-1 expression (p<0.05), but no correlation was found between epidermal growth factor receptor and CR-1 expression. Staining for p53 was observed in 26 (70%) of the carcinomas, 3 (10%) intestinal metaplasias and none of the gastric mucosa samples. This data demonstrate that CR-1, like TGFalpha, may be a tumor marker for a subset of gastric carcinomas in addition to being an important factor in the early stages of gastric cancer development.     

Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas.

Evidence of accumulating for the failure of apoptosis as an important factor in the evolution of colorectal cancer and its poor response to adjuvant therapy. The proto-oncogene bcl-2 suppresses apoptosis. Its expression could provide an important survival advantage permitting the development of colorectal cancer. The expression of bcl-2 and p53 was determined by immunohistochemistry in 47 samples of histologically normal colonic mucosa, 19 adenomas and 53 adenocarcinomas. Expression of bcl-2 in colonic crypts > 5 cm from the tumours was confined to crypt bases but was more extensive and intense in normal crypts < 5 mm from cancers. A higher proportion of adenomas (63.2%) than carcinomas (36.5%) expressed bcl-2 (P < 0.05). A lower proportion of adenomas (31.6%) than carcinomas (62.3%) expressed p53 (P < 0.02). A total of 26.3% of adenomas and 22% of carcinomas expressed both bcl-2 and p53. To determine whether these samples contained cells which expressed both proteins, a dual staining technique for bcl-2 and p53 was used. Only 1/19 adenomas and 2/53 carcinomas contained cells immunopositive for both bcl-2 and p53. Moreover there was evidence of reciprocity of expression of bcl-2 and p53 in these three double staining neoplasms. We suggest that bcl-2 provides a survival advantage in the proliferative compartment of normal crypts and colorectal neoplasms. However, its expression is lost during the evolution from adenoma to carcinoma, whereas p53 expression is increased, an event generally coincident with the expression of stabilised p53, which we presume to represent the mutant form.     

Effects of expression of hRFI on adenoma formation and tumor progression in colorectal adenoma-carcinoma sequence

For colorectal carcinomas as well as colonic polyps we investigated the expression of a newly discovered gene, hRFI, which is isolated by the yeast two-hybrid screening using hTid as a bait and expressed highly in esophageal carcinomas. Immunohistochemical staining was performed on 48 colorectal carcinomas and 77 colorectal polyps consisting of 70 adenomas and 7 hyperplastic polyps using the antibody of hRFI. We analyzed the expression of hRFI and the correlation between the percentage of staining of each and their clinico-pathological characteristics. Protein coding by hRFI was specifically and diffusely expressed in most of the cancerous regions of the colorectum. Also, in the early stage of colorectal adenomas, staining of hRFI was focal, and the percentage area of diffuse staining increased as the degree of dysplasia progressed. Although all normal colorectal glands and most hyperplastic polyps (71.4%) showed no staining of hRFI, most colorectal adenomas and carcinomas (93.2%) showed a focal or diffuse staining (P<0.001). Furthermore, the percentage of diffuse staining in carcinomas (81.3%) was significantly higher than in adenomas (5.7%) (P<0.001). hRFI is highly expressed in colorectal carcinomas. In the adenoma-carcinoma sequence, hRFI is involved at the initial tumor formation and its diffuse expression is associated with colorectal carcinogenesis. This evidence suggests that hRFI may act as an oncogenic molecule affecting the apoptotic pathway.     

Expression of beta-catenin and full-length APC protein in normal and neoplastic colonic tissues

Mutations of the APC gene are thought to be early events in the process of colorectal carcinogenesis. Although the complete function(s) of the APC gene product is not known, it has been shown that the APC protein interacts with beta-catenin in a multi-protein complex to regulate the level of expression of beta-catenin. Loss of normal APC protein function can lead to an accumulation of beta-catenin in the cytosol and the nucleus. Immunohistochemical methods were used to determine the relationship between APC and beta-catenin protein expression in human colonic tissues (150 normal, 9 hyperplastic, 58 adenomas and 83 carcinomas) and 12 paired samples of normal and cancer tissue in mouse colon. In all samples of normal human and mouse colonic mucosa and in human hyperplastic polyps both APC and beta-catenin immunoreactivity were present in colonocytes. APC expression was cytoplasmic, with maximal immunoreactivity in the goblet cells. beta-Catenin expression was predominantly localized to the plasma membrane, with no nuclear immunoreactivity. APC immunoreactivity was absent in all of the mouse adenocarcinomas and 83% of the human colon cancers. All of the human and mouse carcinomas had nuclear and cytoplasmic beta-catenin expression. In contrast, only 29% of the 58 colonic adenomas were completely negative for APC immunoreactivity. Regardless of the presence or absence of APC, all of the adenomas had cytoplasmic and nuclear beta-catenin immunoreactivity. Many colonic adenomas retain expression of full-length APC protein whereas it is usually lost in colorectal cancers. Regardless of the status of APC protein expression, beta-catenin protein was found in the cytoplasm and nucleus of all neoplastic colonic mucosa. The dissociation between loss of expression of APC and accumulation of beta-catenin in the nucleus suggests that inactivation of both alleles of the APC gene may not be required for beta-catenin nuclear accumulation in colonic adenomas.     

Binding of peanut agglutinin (PNA) and Dolichos biflorus agglutinin (DBA) to human colonic carcinomas, adenomas, and polyps: histochemical staining by the lectin-antilectin-PEP method

Binding of 2 lectins--peanut agglutinin (PNA) and Dolichos biflorus agglutinin (DBA)--with human colonic carcinomas, adenomas, juvenile and hyperplastic polyps, and polyps in Cronkhite-Canada syndrome was examined histochemically by the lectin-antilectin-PAP method. With PNA, brush borders of the carcinoma cell were stained(90.9%), while the cytoplasm of the adenomas and polyps were stained granularly (88.0%). With DBA, the cytoplasm of the carcinomas was stained diffusely (72.7%), though 25% of the cases showed the fringed type cytoplasmic staining similar to adenomas, polyps and normal crypts. It appears important to recognize the differences in the staining patterns, especially in PNA, between carcinomas and other benign lesions, which apparently reflect changes of sugar residues during cancerization.     

Interleukin-4 receptor and epidermal growth factor receptor expression in colorectal cancer.

Interleukin-4 receptor (IL-4R) and Epidermal Growth Factor receptor (EGFR) were assessed as factors associated with adenoma-carcinoma progression in colorectal cancer and tumour invasion. A monoclonal antibody (MR6) was applied to detect IL-4R in: metaplastic polyps (five cases), adenomas (15 cases), and carcinomas (44 adenocarcinomas and one squamous cell). Positive labelling was obtained in all polyps, adenomas and in 40/45 carcinomas. Normal colonic mucosa of these patients, as well as macrophages and lymphocytes infiltrating the tumour stroma, were also positively labelled with MR6. Four out of five poorly differentiated adenocarcinomas did not show IL-4 receptor expression. No significant correlation was found with tumour size, lymph node stage and IL-4 receptor expression. On the above specimens a parallel detection of epidermal growth factor receptors (EGFR) by a monoclonal antibody (EGFR 1) was carried out. Expression of EGFR was found in 14/20 polyps and in 22/45 carcinomas. All but one of the EGFR positive malignant tumours showed coexpression of IL-4 receptor. Lymph node involvement by tumour cells was detected in 25 out of 45 patients. Eighteen of these 25 cases were positive with EGFR1.     

Genetic Alterations of Mixed Hyperplastic Adenomatous Polyps in the Colon and Rectum

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K- ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K- ras . No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K- ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.     

Patterns of proliferative changes in crypts bordering colonic tumors: Zonal histology and cell cycle marker expression

Proliferative crypt changes have been noted in mucosa bordering colonic carcinomas, but their biological significance is disputed. We anticipated that zonal patterning of histological changes and cell cycle marker expression would provide clues to the pathogenesis of these border changes. 81 specimens were examined including carcinomas, adenomatours polyps, adenomas with early carcinoma, flat adenomas and aberrant crypt foci. The spatial distribution and frequency of micro-architectural features, and mucosal thickness were determined in a border domain of 150 300 sequential crypts/specimen. Immunocytochemical expression of Ki67 and p53 antigens in crypts also was semi-quantitatively examined. We found that in 100% of carcinomas two histologically abnormal zones (Proximate and Middle) separated tumor from normal mucosa. Differences in the feature frequency between zones were statistically significant (p<0.05). Both zones showed mild increases in crypt cell expression of Ki67, with a statistically significant relationship to zonal patterning (p<0.005). Weak expression of p53 only appeared in rare cells. Crypt elongation with mucosal thickening (1.9x normal, p<0.001) in the Proximate and Middle zones distinguished carcinomas from border changes in all benign lesions, except flat adenomas. Since this change occurs in all cases of carcinoma, there is no correlation with tumor stage or grade. Also in carcinomas, elaborate complexes of attached crypts (connected crypt structures) were characteristic of the Middle zone, so that proximate zone was always architecturally simpler. We conclude, that despite continuous carcinoma growth, the invaded border mucosa maintains a prototypical zonal organization of molecular and histological crypt changes This spatially organized reaction pattern is likely to reflect an interplay between regulated growth and destructive processes in response to advancing carcinoma. Compared to the edges of benign colonic tumors, the edges of carcinomas are distinctive and consistent enough to be diagnostically useful.     

Loss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas

The p53 gene is a tumor suppressor gene located on chromosome 17p. Deletions of this chromosome and point mutations of p53 have been implicated in the development of colonic neoplasms. We have analyzed the loss of heterozygosity of the human p53 tumor suppressor gene in 40 cases of colorectal carcinoma using two restriction fragment length polymorphisms detected by BglII and AccII restriction enzymes. p53 gene product expression was studied immunohistochemically in 64 colorectal carcinomas, 18 adenomas, and 40 normal colonic mucosae using an anti-human p53 monoclonal antibody (Pab 1801) and the avidin-biotin-peroxidase complex technique. Twelve of the 40 patients (30%) were polymorphic for the p53 gene. In ten of these informative patients (83%), the tumor samples showed the loss of one allele when compared with normal colorectal samples of the same patient. One of the homozygous patients showed a loss of both p53 alleles. p53 immunostaining was observed in 43 of 64 carcinomas (67%) but only in two adenomas (11%). These two positive adenomas showed areas of carcinoma in situ. The normal mucosa was always negative. No relation could be found between p53 immunostaining and the degree of differentiation, the extension of the tumor, or the Ki-67 proliferative index. Mucinous carcinomas and right-side carcinomas were less p53 immunoreactive (25% and 52%, respectively) than the usual adenocarcinomas (73%) and distal tumors (72%). These findings suggest that p53 may be a target of chromosome 17 deletions and that this gene may play a role in the malignant transformation of adenomas. BglII and AccII restriction fragment length polymorphism analysis of the p53 gene may be a useful and direct technique to detect allelic loss of this gene in tumors.     

Over-expression of p53 protein in gastric adenoma and cancer

Recently, alterations of p53 gene in gastric cancer have been reported by several authors, but the role of p53-gene alterations in early step of carcinogenesis of gastric cancer remains unclear. To assess whether p53 expression is an early event in the carcinogenesis of gastric cancer, 402 gastric tumors (14 hyperplastic polyps, 48 gastric adenomas, 340 gastric cancers) were analyzed by immunohistochemistry using the specific antibody, PAb1801, against p53 oncoprotein. Five (15%) of 34 adenomas and 110 (32%) of 340 gastric cancers showed a definite positive nuclear staning for p53 protein. In contrast, the anti-p53 MAb did not show any specific staining in normal gastric epithelial cells, intestinal metaplasia or hyperplastic polyps. Out of nine adenomas showing mild dysplasia, only one tumor (11%) showed p53 expression. In contrast, 4 (16%) of 25 adenomas showing moderate dysplasia revealed positive p53 expression. In addition, positive p53 staining was not found in adenomas less than 1 cm in diameter, but five (25%) of 20 adenomas 1 cm or more in diameter showed definite p53-staining. In this way, the positive-p53 tissue status in adenomas was correlated with the dysplastic grade and size of adenomas. The incidence of positive-p53 immunoreaction in the differentiated type of cancers was 35% and showed no relation to wall invasion. On the contrary, p53 expression in the undifferentiated type of m-cancers, in which tumor invasion was limited to the mucosal layers, was detected in only one (5%) of 21 cases. Among undifferentiated type of gastric cancer, however, deeply invasive cancers showed higher p53-positive rate, as compared with m-cancer. These results may suggest p53 gene activation at a relatively early stage of the adenoma-carcinoma sequence, leading to the development of some differentiated adenocarcinomas in the stomach.     

Subepithelial myofibroblasts express cyclooxygenase-2 in colorectal tubular adenomas.

PURPOSE: Recent data support the hypothesis that the inducible isoform of cyclooxygenase (COX-2) plays a role in the early stages of colonic carcinogenesis and that nonsteroidal anti-inflammatory drugs (NSAIDs) retard the development of colon cancer by modulating COX-2. However, the cell types responsible for producing COX-2 in colorectal adenomas remain a subject of controversy. EXPERIMENTAL DESIGN: COX-2 expression in normal colonic mucosa (n = 50), hyperplastic polyps (n = 43), sporadic adenomas (n = 67), and invasive colonic adenocarcinoma (n = 39) was studied in formalin-fixed and paraffin-embedded tissue sections from endoscopy biopsy and colonic resection specimens. Immunohistochemistry (avidin-biotin complex technique with double immunolabeling) was used to identify the phenotypes of COX-2-producing cells. RESULTS: In colorectal adenomas, increased expression of COX-2 was detected and localized to alpha smooth muscle actin ( proportional, variant SMA)-positive subepithelial stromal cells (myofibroblasts) in the periluminal region of the lamina propria in 63 (94%) of 67 cases. In contrast, in normal colonic mucosa and in hyperplastic polyps with intact epithelium, COX-2 expression was found only in macrophages and endothelial cells. In areas in which the surface epithelium was ulcerated in normal mucosa as well as hyperplastic or neoplastic polyps, COX-2 expression was increased in granulation tissue (and present in macrophages, endothelium, and myofibroblasts). In invasive carcinoma, COX-2 expression in myofibroblasts was limited to the adenomatous portion of the tumor and was detected in 62% of cases (n = 39). In addition, focal expression of COX-2 by malignant epithelial cells was observed in 23% of invasive adenocarcinoma. CONCLUSIONS: These results show that increased COX-2 expression in sporadic adenoma of the colon is common and is localized specifically to subepithelial intestinal myofibroblasts. These findings further support the hypothesis that myofibroblasts are important target cells for NSAID-mediated chemoprevention of colorectal cancer.     

p53蛋白检测用于早期发现大肠癌

应用石蜡切片免疫组织化学方法，检测了p53在112例人大肠息肉中的表达，其中26例为腺癌癌变。71例腺癌中3例（4％）P53表达阳性。增生性息肉和轻度不典型增生腺瘤53表达均为阴性。p53表达随腺癌不典型增生程度的不断加重而增强。腺瘤癌变时表达率升高达88％（P＜0．001）。绒毛状腺癌的p53表达率显著增高（p＜0．05）。结果表明在大肠肿瘤形成过程中p53基因实变的作用在良性腺瘤转变为癌的阶段，可能在腺瘤恶变中起关键作用。故p53的检测时判断腺瘤的癌变倾向有重要意义，能辅助临床病理诊断，早期发现大肠癌．     

Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer.

Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 non-adenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100% of the carcinomas, in 100% of the adenomas and in 37.5% of the non-adenomatous polyps, i.e. all ten lesions with a normal karyotype were histologically diagnosed as hyperplastic polyps. Although adenomas and carcinomas shared several karyotypic features, two chromosome aberrations, der(8;17)(q10;q10) and -14, were found in carcinomas but not in adenomas, indicating that they might be specifically associated with carcinoma development in the large bowel mucosa. The karyotypic similarity seen between the malignant and benign tumours in the same patient, and also sometimes among non-malignant polyps in the same case, indicates that these microscopically distinct lesions may be part of a single neoplastic clonal expansion.     

High mobility group HMGI(Y) protein expression in human colorectal hyperplastic and neoplastic diseases

HMGI(Y) proteins are overexpressed in experimental and human malignancies, including colon, prostate and thyroid carcinomas. To determine at which step of the carcinogenic process HMGI(Y) induction occurs, we analysed the expression of the HMGI(Y) proteins in hyperplastic, preneoplastic and neoplastic tissues of colorectal origin by immunohistochemistry. All the colorectal carcinomas were HMGI(Y)-positive, whereas no expression was detected in normal colon mucosa tissue. HMGI(Y) expression in adenomas was closely correlated with the degree of cellular atypia. Only 2 of the 18 non-neoplastic polyps tested were HMGI(Y)-positive. These data indicate that HMGI(Y) protein induction is associated with the early stages of neoplastic transformation of colon cells and only rarely with colon cell hyperproliferation.     

Angiogenesis and p53 expression in the colorectal adenoma-carcinoma sequence

Angiogenesis, the formation of new vessels, is essential for tumor growth and metastasis. Mutations of p53 tumor suppressor gene are frequent and play an important role in colorectal oncogenesis. A role of p53 as an angiogenesis inhibitor has also been proposed. We evaluated angiogenesis and p53 expression in 16 hyperplastic polyps, 35 solitary tubular and tubulovillous adenomas, and 47 cases of sporadic colorectal carcinomas arising on the basis of preexisting adenomas, with standard immunohistochemical techniques. The mean microvessel density (MVD) in carcinomas was significantly higher compared with the respective adenomatous part of the same tumor (27.9 vs. 7; P=0.0001). Linear regression analysis of MVD between cancerous and adenomatous areas showed a significant correlation (P = 0.0001, r = 0.56), raising the possibility that carcinomas arising from better vascularized adenomas might show increased vascularity. The MVD was significantly higher in stage C compared with stage A cases (P=0.04). p53 positivity was detected in 26 of 47 cancerous (55%) and in 14 of 47 adenomatous areas (30%; P = 0.0002). All carcinomas arising from p53-positive adenomas were also p53 positive. p53 positivity associated with a higher MVD in adenomas (P = 0.02), but not in carcinomas (P = 0.78). We conclude that angiogenesis and p53 play a critical role in colorectal neoplasia, and the process of malignant transformation in tumors arising from highly angiogenic adenomas, particularly those carrying p53 mutations, is accelerated with rapid tumor progression from stage to stage, indicating a more aggressive tumor phenotype.     

Expression of epidermal growth factor-receptor related protein (ERRP) in human colorectal carcinogenesis

We hypothesize that ERRP (EGFR-related protein), a recently identified negative regulator of EGFR may modulate EGFR function in colorectal carcinogenesis. The expression of ERRP and EGFR in normal and neoplastic colorectal tissue was examined. ERRP was highly expressed in normal colonic mucosa and benign colorectal adenomas, but lower in colorectal cancer. Mean scores for ERRP expression decreased significantly across well differentiated, moderately well differentiated and poorly differentiated (P = 0.002) tumors, respectively. ERRP expression became more attenuated in polyps with increasing grades of dysplasia. In contrast, expression of EGFR was inversely related to ERRP in representative samples of normal and neoplastic tissues.     

p53 expression in oral cancer: observations of a South Indian study

Oral cancers constitute a significant proportion of hospital admissions among cancer patients in India. The aim of this study was to elucidate the role of tumour suppressor gene p53 in the pathogenesis of oral squamous cell carcinoma by immunohistochemistry. Though extensive studies on p53 alterations in oral cancers have been done in Western countries and some Asian countries, only a few studies have emerged from India, especially the Southern states. This study would therefore be helpful in providing an Indian perspective, with particular reference to South Indian states. A total of 110 cases of oral squamous cell carcinoma, 35 dysplastic lesions, 15 hyperplastic lesions, and 50 samples of normal mucosa were assessed for p53 expression. Out of 110 cases of oral carcinoma, 40 (36%) were p53 positive. Among 35 cases of dysplastic lesions studied, 6 (17%) showed p53 positive staining. None of the hyperplastic lesions and normal oral lesions showed any evidence of p53 positivity. However, in 9 out of 40 (23%) cases of positive infiltrating squamous cell carcinomas, the adjacent or overlying non-tumourous epithelium demonstrated focal areas of p53 positive staining in the basal and parabasal layers of the epithelium. In addition, in 7 out of 110 (6%) cases, cytoplasmic staining was observed. In these samples, nuclei were not stained. Our results indicate that p53 over-expression may be involved in only a certain proportion of oral carcinomas. The fact that 6% of the dysplastic lesions were p53 positive, and adjacent non-tumourous epithelium of 23% infiltrating squamous cell carcinomas showed positive staining for p53 in the progenitor compartment of the epithelium indicates that p53 immunoreactivity could be used to detect early tumours as well.     

Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps

Altered mucin glycosylation and the de novo appearance of gastric mucin antigens have been described in colonic adenomas. The purpose of our study was to determine if expression of the gastric mucin genes MUC5AC and MUC6 occurs in colorectal adenomas and whether this correlates with histopathologic criteria of malignant potential. Immunohistochemical staining using antibodies against MUC5AC and MUC6 tandem repeat synthetic peptides was performed on specimens of normal colon mucosa (n = 26), hyperplastic polyps (n = 9) and adenomatous polyps (n = 111). Mucin mRNA levels were determined using RNase protection assays using riboprobes corresponding to unique non‐repetitive sequences. MUC5AC and MUC6 staining were rarely detected and of low intensity in normal colon and hyperplastic polyps. The number of immunoreactive polyps and intensity of MUC5AC and MUC6 staining were greatest in larger adenomas of moderate villous histology and dysplasia. MUC5AC and MUC6 staining tended to decrease in highly villous polyps with severe dysplasia. Increased MUC5AC mRNA levels were found in 26/45 of adenomas tested compared with 0/9 normal colon specimens. MUC6 mRNA levels were found in 20/45 of adenomas compared with 1/9 normal colon specimens. MUC5AC and MUC6 mRNA were present more frequently and at higher levels in polyps with intermediate stages of size, villous histology and dysplasia. We conclude that aberrant expression of MUC5AC and MUC6 mucin genes is likely responsible for an expanded repertoire of mucin antigen expression in colorectal neoplasia. Int. J. Cancer 80:210–218, 1999. Published 1999 Wiley‐Liss, Inc.     

The value of epidermal growth-factor receptor (egfr) as a tumor-marker for human oral premalignant and malignant lesions

A previous study demonstrated increased epidermal growth factor receptor (EGFR) in oral dysplasia while another showed decreased EGFR in oral dysplasia. The present study examined immunohistochemical expression of EGFR in 33 dysplastic oral lesions as well as in 9 normal oral mucosa specimens, 12 hyperplastic oral lesions and 10 oral squamous cell carcinomas (SCCs). There were no significant differences in EGFR staining either in intensity or in the epithelial layers stained among the normal oral epithelium, hyperplastic and dysplastic lesions. In addition, no significant difference was noted between keratinized and non-keratinized specimens and among lesions from different sites. Oral SCCs demonstrated significantly stronger staining than the normal oral mucosa, hyperplastic and dysplastic lesions (p=0.0011). At this time, the conflicting data on the EGFR expression in oral dysplastic lesions indicate that this receptor is not a good marker for oral dysplasia. Because most of the available data (including our results) show that the majority of oral SCC overexpress EGFR, this receptor may be useful in the diagnosis and treatment of some oral cancers.     

Quantitative analysis of colorectal mucosal lesions by autofluorescence endoscopy: discrimination of carcinomas from other lesions

A newly developed auto?uorescence (AF) imaging technique was applied during colonoscopy in a clinical setting. This pilot study was conducted to evaluate the clinical feasibility of applying AF endoscopy for distinguishing colorectal lesions. A total of 54 colorectal mucosal lesions obtained from 43 patients who underwent both white-light and AF endoscopy and were treated by endoscopy or surgery were assessed. Of the lesions, 11 were hyperplastic polyps, 30 were adenomas and 13 were carcinomas. To quantify the AF intensity, a color-contrast index (CCI) was determined and evaluated in relation to the histology, size and shape of each lesion. CCI was significantly associated with the histology and size of the lesions, but not their shape. CCI increased as the malignant potential increased (in the order of hyperplastic polyps→adenomas→carcinomas), irrespective of the lesion size (r=0.797, p<0.0001 for size>8 mm; r=0.622, p=0.0045 for size>8 mm but >15 mm; r=0.644, p=0.0071 for size>15 mm). In each size group, CCI tended to be higher for carcinomas than for adenomas, and also higher for adenomas than for hyperplastic polyps. CCI allowed discrimination of adenomas/carcinomas from hyperplastic polyps with 95.3% sensitivity and 63.6% specificity (cut-off value, 14.5), and of colorectal carcinomas from adenomas with 84.6% sensitivity and 80.0% specificity (cut-off value, 28.0). These results suggest that the quantitative analysis of AF intensity using CCI is helpful to discriminate among different types of colorectal mucosal lesions, including carcinomas.