Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

C-MYC, HIF-1α, ERG, TKT, and GSTP1: an Axis in Prostate Cancer?

To analyze putative biomarkers for prostate cancer (PCA) characterization, the second leading cause of cancer-associated mortality in men. Quantification of the expression level of c-myc and HIF-1α was performed in 72 prostate cancer specimens. A cohort of 497 prostate cancer patients from The Cancer Genome Atlas (TCGA) database was further analyzed, in order to test our hypothesis. We found that high c-myc level was significantly associated with HIF-1α elevated expression (p = 0.008) in our 72 samples. Statistical analysis of 497 TCGA prostate cancer specimens confirmed the strong association (p = 0.0005) of c-myc and HIF-1α expression levels, as we found in our series. Moreover, we found high c-myc levels significantly associated with low Glutatione S-transferase P1 (GSTP1) expression (p = 0.01), with high Transketolase (TKT) expression (p < 0.0001). High TKT levels were found in TCGA samples with low GSTP1 mRNA (p < 0.0001), as shown for c-myc, and with ERG increased expression (p = 0.02). Finally, samples with low GSTP1 expression displayed higher ERG mRNA levels than samples with high GSTP1 score (p < 0.0001), as above shown for c-myc. Our study emphasizes the notion of a potential value of HIF-1α and c-myc as putative biomarkers in prostate cancer; moreover TCGA data analysis showed a putative crosstalk between c-myc, HIF-1α, ERG, TKT, and GSTP1, suggesting a potential use of this axis in prostate cancer.

Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study.

BACKGROUND: The benefits of prophylactic central compartment lymph node dissection (pCCND) in papillary thyroid cancer (PTC) are still under investigation. This treatment seems to reduce PTC recurrence/mortality rates but has a higher risk of surgical complications. The lack of prospective randomized trials does not allow definitive recommendations. The aim of this prospective randomized controlled study was to evaluate the clinical advantages and disadvantages of pCCND. PATIENTS: A total of 181 patients with PTC without evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or Group B (n = 93) and treated with TTx + pCCND. RESULTS: After 5 years of followup, no difference was observed in the outcome of the two groups. However, a higher percentage of Group A were treated with a higher number of (131)I courses (P = .002), whereas a higher prevalence of permanent hypoparathyroidism was observed in Group B (P = .02). No preoperative predictors of central compartment lymph node metastases (N1a) were identified. Only three patients were upstaged, and the therapeutic strategy changed in only one case. CONCLUSIONS: cN0 patients with PTC treated either with TTx or TTx + pCCND showed a similar outcome. One advantage of TTx + pCCND was a reduced necessity to repeat (131)I treatments, but the disadvantage was a higher prevalence of permanent hypoparathyroidism. Almost 50% of patients with PTC had micrometastatic lymph nodes in the central compartment, but none of the presurgical features analyzed, including BRAF mutation, was able to predict their presence; moreover, to be aware of their presence does not seem to have any effect on the outcome.

Primary retroperitoneal müllerian adenocarcinoma: a case report and literature review.

Primary retroperitoneal müllerian adenocarcinoma (PRMA) is an extremely rare clinical entity. We report the case of a 54-year-old woman who presented with a mass in the right lower retroperitoneum, identified during an ultrasound exam. Computed tomography confirmed a retroperitoneal mass measuring 11 cm. The patient underwent laparotomy and the mass was completely excised. The histopathological exam revealed PRMA.

Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results from a series of 505 consecutive patients.

OBJECTIVE: The cytological patterns of follicular and Hupsilonrthle cell nodules are included among the indeterminate results of fine-needle aspiration cytology, because distinction between benign and malignant lesion can only be made on histological criteria. The diagnostic value of atypia at cytology, clinical parameters and echographic patterns were examined to establish the risk of malignancy in 505 patients with follicular and Hupsilonrthle cell thyroid nodules at cytology. DESIGN AND PATIENTS: The study included 505 consecutive patients who had undergone thyroidectomy from the period 2002-2005. RESULTS: Histological diagnosis of malignancy was carried out in 125 of 505 (25%) patients, the follicular variant of papillary carcinoma being the most frequent histotype. Only atypia at cytology (P < 0.0001) and spot microcalcifications at ultrasound (P = 0.009) were predictive of malignancy. Male gender, normal thyroid volume, single nodularity, nodule hypoechogenicity, size and blurred margins were associated with malignancy, although not significantly. An arbitrary clinical score allowed the identification of patients with high (41%, 110 patients) and low (16%, 242 patients) risk of malignancy. Combining the clinical score with the presence of atypia at cytology we could identify 30 patients (6%) in whom the risk of malignancy was as high as 63%. CONCLUSIONS: Twenty-five per cent of patients with a cytological result of follicular and Hupsilonrthle cell thyroid lesion had a final diagnosis of malignancy. Only atypia at cytology and spot microcalcifications at thyroid ultrasound were significantly associated with malignancy. Other clinical parameters and thyroid ultrasound patterns can be used to set up a clinical score useful for predicting the individual risk of malignancy before surgery.

Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature.

Recently, a somatic point mutation of the B-RAF gene (V600E) has been identified as the most common genetic event in papillary thyroid carcinoma (PTC), with a prevalence variable among different series. Since discordant data on the clinico-pathologic features of B-RAF mutated PTC are present in the literature, the aim of the present co-operative study was to establish the prevalence of this genetic alteration and to perform a genotype-phenotype correlation in a large cohort of patients with PTC. To this purpose, a series of 260 sporadic PTCs with different histological variants were included in the study. The mutational analysis of the B-RAF gene was performed either by RT-PCR followed by single-stranded conformational polymorphism or by PCR and direct sequencing. Statistical analyses were obtained by means of chi2/Fisher's exact test and t-test. Overall, a heterozygous T > A transversion at nucleotide 1799 (V600E) was found in 99 out of 260 PTCs (38%). According to the histological type of the tumor, the B-RAF (V600E) mutation was present in 48.3% of cases of classic PTCs (85 out of 176), in 17.6% (nine out of 51) of follicular variants of PTCs, in 21.7% (five out of 23) in other PTC variants and in none of the ten poorly differentiated tumors. B-RAF (V600E) was significantly associated with the classic variant of PTC (P = 0.0001) and with an older age at diagnosis (P = 0.01). No statistically significant correlation was found among the presence of B-RAF (V600E) and gender, tumor node metastasis (TNM), multicentricity of the tumor, stage at diagnosis and outcome. In conclusion, the present study reports the prevalence of B-RAF (V600E) (38%) in the largest series of sporadic PTCs, including 260 cases from three different Italian referring centers. This prevalence is similar to that calculated by pooling together all data previously reported, 39.6% (759 out of 1914 cases), thus indicating that the prevalence of this genetic event lies around 38-40%. Furthermore, B-RAF (V600E) was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated PTC variants. A significant association of B-RAF mutation was also found with an older age at diagnosis, the mutation being very rare in childhood and adolescent PTCs. Finally, no correlation was found with a poorer prognosis and a worse outcome after a median follow-up of 72 months.

Prognostic significance of osteopontin expression in early-stage non-small-cell lung cancer.

Osteopontin (OPN) is a multifunctional protein, which has recently been shown to be linked to tumorigenesis, progression and metastasis in different malignancies. Since non-small-cell lung cancer (NSCLC)'s prognosis remains bad, with few predictors of outcome, the purpose of this study was to evaluate if OPN might be involved in NSCLC's biology and therefore represent a prognostic marker and a target for new therapeutic trials. Immunohistochemistry was used to detect OPN expression, evaluated as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide cohort of patients with stage I NSCLC (136 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumours with low (<20%) from tumours with high (> or =20%) OPN expression. A statistically significant correlation between high levels of OPN and shorter overall (P = 0.034) and disease-free (P = 0.011) survival in our patients was shown. Our results support the hypothesis that high OPN expression is a significantly unfavourable prognostic factor for the survival of patients with stage I NSCLC. This conclusion has notable importance in terms of the biological characterization of early-stage tumours and therapeutic opportunities.

Type I interferons modulate the expression of thyroid peroxidase, sodium/iodide symporter, and thyroglobulin genes in primary human thyrocyte cultures.

We evaluated in primary human thyrocyte cultures the effect of interferon (IFN)-alpha and -beta on the expression of thyroid peroxidase (TPO), sodium/iodide symporter (NIS), and thyroglobulin (Tg) as well as T(4) release. Human thyrocyte cultures were carried out with fresh normal thyroid tissue. Gene and protein expression of Tg, TPO, and NIS were assessed by RT-PCR and Western blot analysis after 24, 48, and 72 h of treatment with TSH alone (10 mIU/ml) and in combination with IFN alpha or -beta (10(4) U/ml). IFN inhibited the TSH-stimulated gene expression of Tg, TPO, and NIS in a time-dependent manner without significant differences between IFN alpha and -beta. Moreover, the addition of both type I IFNs clearly reduced the TSH-stimulated protein expression of Tg, TPO, and NIS after 72 h of exposure. Finally, this down-regulation was associated with a reduction of T(4) release by almost 50%. In conclusion, our study shows that both IFN alpha and -beta down-regulate the TSH-stimulated expression of Tg, TPO, and NIS as well as T(4) release. Indeed, the development of hypothyroidism during type I IFN therapy may be related, at least in part, to an abnormal expression and function of key proteins involved in iodine uptake and organification.

Spontaneous short-term remission of primary hyperparathyroidism from infarction of a parathyroid adenoma.

We report a 39-yr-old woman with spontaneous short-term remission of primary hyperparathyroidism (PHPT). She was referred to our Department for PHPT with bilateral kidney stones diagnosed elsewhere; at the time of our observation she had developed anterior neck pain associated with swelling and tenderness. Biochemical data (serum ionized calcium and PTH) suggested a remission of the PHPT. The local symptoms gradually improved and disappeared over the next several days without therapy. Serum ionized calcium and PTH levels remained normal for up to 11 months. Subsequently, the patient had a recurrence of PHPT with mild hypercalcemia and elevated PTH levels. The patient underwent surgery and pathological examination revealing a 1.0 x 1.2 cm parathyroid adenoma with areas of necrosis with hemosiderinladen macrophages. In conclusion, we describe a case of spontaneous short-term remission of PHPT due to infarction of parathyroid adenoma.

Thyroid papillary carcinoma: preliminary evidence for a germ-line single nucleotide polymorphism in the Fas gene.

The expression of Fas in thyroid tumours and Graves' disease was analysed by mRNA transcript expression. As compared with unaffected thyroid tissue, Fas expression was enhanced in Graves' disease, adenomas, and papillary and follicular carcinomas. This pattern was also reflected in immunohistochemical studies. The PCR single-strand conformational polymorphism (SSCP) method and DNA sequencing were used to analyse Fas exons 1-9. The study was carried out on five different histotypes of thyroid tumours (n=93) and tissue from Graves' disease patients. As compared with a group of healthy blood donors (n=64), a significant association (P=0.006) emerged between papillary thyroid carcinoma and a silent single nucleotide polymorphism (SNP, 988C-->T) in exon 7 of the Fas gene. Other forms of thyroid pathology were not associated with the above polymorphism. Patients with neoplasia showed the same SNP in tumour tissue, in the unaffected contralateral thyroid lobe, and in peripheral blood cells. Thus, the 988C-->T polymorphism appeared to be of germ-line origin.

Video assisted prophylactic thyroidectomy and central compartment nodes clearance in two RET gene mutation adult carriers.

Activating point mutations of RET gene have been demonstrated to be causative of the familial form of medullary thyroid cancer (MTC), both isolated (FMTC) and associated to other endocrine neoplasia [multiple endocrine neoplasia (MEN) 2A and 2B]. In RET gene mutation carriers, who are prone to developing MTC, prophylactic thyroidectomy is recommended to obtain their definitive cure. The simultaneous excision of the central node compartment is mandatory when the stimulation pentagastrin test for serum calcitonin is positive. Although the minimally invasive video assisted thyroidectomy (MIVAT) is nowadays currently adopted in many centers, it has never been employed for the prophylactic thyroidectomy of RET gene mutation carriers. The fear of obtaining an incomplete lymphadenectomy of the central compartment was the main reason for this reluctance. Since RET gene mutation carriers have often normal thyroid volume and, if involved, small lymph nodes, they indeed represent the best candidates to this approach especially when considering that they are usually young and concerned about the cosmetic results and the period of hospitalization. The excellent results obtained by MIVAT in the last few years induced us to propose this procedure together with a central compartment lymphadenectomy to 2 RET gene mutation carriers recently found by genetic screening. As assessed by a negative pentagastrin stimulation test performed after 6 months from the MIVAT, they were definitively cured without any surgical complication with the exception of a transient hypoparathyroidism. They showed a great satisfaction for both the cosmetic results and the very short period of hospitalization, thus supporting the idea that MIVAT can be used in association with the central node dissection for the prophylactic treatment of RET mutation gene carriers whose thyroid volume is still normal.

Plasma and tissue chromogranin in patients with adrenocortical adenomas.

Adrenal adenomas frequently arise from cortical islets in the medulla, and these islets seem to present a greater risk for pathological growth than cortical cells within the adrenal cortex. Chromogranin A (CgA), a glycoprotein co-stored in secreting granules and co-released with resident hormones of chromaffin cells, behaves as a prohormone, generating several biologically active peptides capable of influencing growth, morphogenesis and progression of endocrine tumors. The aim of our study was to investigate whether chromaffin cells may be involved in the development and growth of adrenocortical adenomas. We enrolled 19 patients (12 females and 7 males, mean+/-SD age 54.9+/-11.2 yr, age range 34-75 yr) with incidental, non-functioning, benign adrenocortical adenomas, and measured circulating levels of CgA, catecholamines and creatinine before and 2 months after surgery. Plasma CgA was evaluated by immunoradiometric assay. Testing for CgA immunoreactivity in the removed tissues was performed by immunohistochemical analysis. Mean plasma CgA did not significantly change following surgery (before 73.7+/-15.2 ng/ml; after 68.9+/-14.8 ng/ml). Individual CgA values indicated that 4 patients had plasma CgA levels above our cut-off of normality. After mass removal, CgA further increased in 2 cases, decreased in 1 and normalized in 1. No variation in CgA levels was found in the other patients. No correlation was observed between CgA and the variables measured, except between CgA and plasma creatinine (r=0.472, p<0.05). Histopathological evaluation revealed adrenocortical adenomas in all cases and immunohistochemical analysis detected no CgA immunoreactivity in any specimen. Our results show that in human adrenocortical adenomas CgA is not expressed and that removal of the mass does not modify plasma CgA levels. For these reasons the endocrine involvement of local CgA in adrenocortical tumorigenesis is unlikely.

Leiomyosarcoma of the popliteal artery: case report and review of the literature.

Vascular leiomyosarcomas are rare tumors, and only 21 have been described as developing in the systemic arteries. We present a case, the sixth in the literature, of a leiomyosarcoma originating in the popliteal artery of a 67-year-old woman treated with en bloc excision of the neoplasia and the artery followed by a popliteal tibioperoneal trunk bypass. The patient then was underwent adjuvant radiotherapy and chemotherapy. After 31 months of follow-up, the patient has mild claudication but does not have either recurrence or metastasis.

Evaluation of telomerase in the development and progression of colon cancer.

Telomerase activity, a cardinal requirement for immortalization, is a crucial step in the development of cancer and has been studied in many kinds of malignant tumours for clinical diagnostic and/or prognostic utilities. Using a PCR-based TRAP assay, we investigated telomerase activity in 8 adenomatous polyps, 9 dysplastic polyps, and in 36 paired cancer-normal mucosa specimens, one liver and one spleen metastasis from patients resected for sporadic colorectal cancer. Telomerase was absent or very low in normal mucosa and in adenomatous polyps. Dysplastic polyps and adenocarcinoma samples showed telomerase activity, with higher levels in cancer tissues compared to dysplastic lesions. A high telomerase activity was shown to be associated with late-staged cancers and metastasis, providing arguments supporting the role of telomerase not only in the development but also in the progression of colorectal carcinoma. Moreover, telomerase evaluation may help to confirm the malignant transformation in polypoid colorectal lesions with different levels of dysplastic alterations.

Evaluation of telomerase mRNA (hTERT) in colon cancer.

Telomerase activation, a cardinal requirement for immortalization, is a crucial step in the development of malignancy and requires the induction of the catalytic component, human telomerase reverse transcriptase (hTERT), encoded by the hTERT gene. By reverse transcription-PCR, using primers within the reverse transcriptase domain of hTERT, we investigated telomerase messenger in 8 adenomatous and 9 dysplastic polyps, and in 32 paired cancer-normal mucosa specimens, one liver and one spleen metastasis from patients resected for sporadic colorectal cancer. Telomerase messenger was absent or very low in normal mucosa and in adenomatous polyps. Dysplastic polyps and adenocarcinoma samples showed hTERT mRNA, with higher levels in cancer tissues compared to dysplastic lesions. A high telomerase messenger level was shown to be associated with late-staged cancers and with metastasis; thus, detection of telomerase messenger may be useful in the early diagnosis of colon cancer, and telomerase may be a new target for therapeutic intervention.

Neoangiogenesis in colon cancer: correlation between vascular density, vascular endothelial growth factor (VEGF) and p53 protein expression.

Angiogenesis is an essential requirement for the development, progression and metastasis of malignant tumors. Vascular endothelial growth factor (VEGF) plays an essential role in the development of angiogenesis of numerous solid malignancies, including colon cancer. The tumor suppressor gene p53 is a potent transcriptional regulator of genes which are involved in many cellular activities, including cell-cycle arrest, apoptosis and angiogenesis. In order to better understand the relation among p53 status, VEGF expression and microvessels count (MVC) in colon cancer, we evaluated immunoreactivity for CD34 endothelium-associated antigen, VEGF and p53 proteins in 43 cases of colon adenocarcinoma. Our results demonstrated an association between VEGF expression, p53 status and angiogenesis, suggesting that mutant p53 plays a central role in promoting angiogenesis in colon cancer progression.

A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma.

It has been widely demonstrated that neo-angiogenesis and its mediators (i.e. vascular endothelial growth factor), represent useful indicators of poor prognosis in non small cell lung carcinoma. In order to verify whether neovascularization and vascular endothelial growth factor may be considered useful markers of clinical outcome also in the small cell lung cancer subgroup, we retrospectively investigated a series of 75 patients with small cell lung carcinoma treated by surgery between 1980 and 1990. Immunohistochemically-detected microvessels and vascular endothelial growth factor expressing cells were significantly associated with poor prognosis, as well as with nodal status and pathological stage. In fact, patients whose tumours had vascular count and vascular endothelial growth factor expression higher than median value of the entire series (59 vessels per 0.74 mm(2) and 50% of positive cells, respectively), showed a shorter overall and disease-free survival (P=0.001, P=0.001; P=0.008, P=0.03). Moreover, the presence of hilar and/or mediastinal nodal metastasis and advanced stage significantly affected overall and disease-free interval (P=0.00009, P=0.00001; P=0.0001, P=0.00001). At multivariate analysis, only vascular endothelial growth factor expression retained its influence on overall survival (P=0.001), suggesting that angiogenic phenomenon may have an important role in the clinical behaviour of this lung cancer subgroup.

Identification of Fas (APO-1/CD95) and p53 gene mutations in non-small cell lung cancer.

Fas (APO-1/CD95) is a broadly expressed death receptor involved in a series of physiological and pathological apoptotic processes. One of the possible mechanisms for resistance to apoptosis signaling in the immune system as well as in the pathogenesis of non-lymphoid malignancies is the presence of Fas mutations within the entire gene. We investigated, in 79 non-small cell lung cancer (NSCLC) samples, the promoter and the entire coding region of the Fas gene by polymerase chain reaction, single strand conformation polymorphism and DNA sequencing in order to detect putative alterations. Sixteen of 79 tumor samples (20.2%) were found to have Fas alterations, either in promoter or exon region. Since the loss of Fas apoptotic function might be linked to p53 alterations, which are often involved in the development of NSCLC, we analyzed p53 status in 40 of the 79 NSCLC samples. p53 mutations were found to be more frequently present than Fas gene alterations (25 out of 40 cases, 62.5%). These data increase the knowledge regarding mutations of apoptosis-genes involved in the pathogenesis of NSCLC, and give benefits for the clinical management of this type of tumor.

Alterations of Fas (APO-1/CD 95) gene and its relationship with p53 in non small cell lung cancer.

The Fas (APO-1/CD95) system regulates a number of physiological and pathological processes of cell death. The ligand for Fas induces apoptosis by interacting with a transmembrane cell surface Fas receptor. The key role of the Fas system has been studied mostly in the immune system, but Fas mutations, one of the possible mechanisms for resistance to apoptosis signaling, may be involved in the pathogenesis of non-lymphoid malignancies as well. To better understand the potential involvement of Fas system in non-small cell lung cancer (NSCLC) we evaluated Fas and Fas-ligand mRNA expression by polymerase chain reaction in 102 tumor samples and in 44 normal surrounding tissues. Although over 60% of the human NSCLC analysed expressed both genes, they seem to be unable to induce apoptosis in vivo by autocrine suicide. In this regard, we investigated in 79 cases, the promoter and the entire coding region of the Fas gene by polymerase chain reaction, single strand conformation polymorphism and DNA sequencing for detecting putative alterations. Sixteen tumors (20.25 %) were found to have Fas alterations, in promoter and/or exon region. In all cases samples carried heterozygous alterations and mostly showed simultaneous mutations of p53 gene. Moreover, the quantitative analysis of Fas mRNA expression showed high levels of Fas messenger associated with p53 wild-type status alone. Taken together, these findings point to an involvement of Fas/Fas-ligand system in the development of NSCLC, suggesting that the loss of its apoptotic function might be linked to p53 alterations which contribute to the self-maintenance of cancer cells.

[Clinical significance of a carcinogenesis model of colorectal carcinoma]. / Importanza clinica di un modello di carcinogenesi nel carcinoma del colon-retto.

OBJECTIVE: Carcinoma of the rectal colon begins as a small neoplastic polyp which gradually increases in size and, after passing through various degrees of dysplasia, develops into an overtly malignant carcinoma. Clinical experience suggests that patients may be divided into subgroups based on the aggressivity of the tumour. The genetic mutations associated with colorectal cancer have been studied and it is known that the genes primarily responsible for biological changes in the tumour cell, in the early stages, are APC, hMSH2, k-ras2 and, in particular, p53. Indeed, the mutation at the level of gene p53 has been recognized as the most common mutation in tumour cells. The aim of this study was investigate the role of p53 and CD34 in colorectal cancer. METHODS: We studied p53 positivity using immunohistological methods and compared our results with the site, stage (using the TNM system) and histological grade of the tumour. We evaluated CD34 positivity using the same methods in order to detect and quantity the presence of angiogenesis in colorectal cancer. RESULT: P53 was found to be markedly raised in the T3 stage of colorectal cancer, while its expression was decreased in stage T2 and stage T1 carcinomas and it was not detectable in adenomas. These results suggest a close correlation between the tumour stage and the expression of p53. An analogous correlation was found between CD34 expression and angiogenesis. CONCLUSION: The overexpression of p53 in epithelial cells and raised angiogenesis (as reflected in CD34 levels) in stromal cells could represent useful prognostic factors in the management of colorectal cancer.