Clinical outcome of low- and high-risk malignant colorectal polyps: results of a population-based study and meta-analysis of the available literature.

Some histological features of malignant polyps have been used to classify patients into low- and high-risk groups. This study proposed to evaluate the impact of this classification on the clinical outcome of patients with malignant polyps. Through the Colorectal Cancer Registry, 105 patients with endoscopically removed malignant polyps were selected. The presence of one of the following histological features defined malignant polyps as high-risk: infiltrated resection-margin, poorly differentiated carcinoma, lymphatic/vascular invasion and tumour budding and depth of submucosal invasion. Available literature was reviewed by applying a similar classification. Most of the malignant polyps were pedunculated and were localized in the left colon. Fifty-five malignant polyps were classified as low-risk lesions and 50 as high-risk. None of the patients at low-risk died of colorectal cancer. Of the patients at high-risk, three died of cancer; all three cases showed lymphatic/vascular invasion. Review of the literature reveals that an unfavourable clinical outcome is significantly more prevalent in the high-risk compared with the low-risk group (p > 0.005). Moreover, all histological risk factors show a specific predictive value of clinical adverse outcome. Our study and the pooled data analysis confirmed the usefulness of the subdivision into low- and high-risk malignant polyps for management of patients with endoscopically removed colorectal carcinoma.

Lymph node micrometastasis and survival of patients with Stage I (Dukes' A) colorectal carcinoma.

OBJECTIVE: Although patients with Stage I colorectal cancer show an excellent prognosis, a few of them die of metastatic disease. In this subgroup of individuals, the search of occult metastasis might reveal that early dissemination of tumor cells could be the cause of cancer progression. MATERIAL AND METHODS: Through a Cancer Registry, we selected all patients with Stage I disease who died of metastatic tumor; a total of 32 patients were identified and in 25 of them paraffin-embedded material was available. The group was matched to 70 Stage I patients with favorable prognosis (controls). In cases and controls resected lymph nodes were cut, and micrometastases were searched using pan-cytokeratin antibodies. RESULTS: Micrometastases were detected in 18 of 25 (72%) Stage I patients who died of the disease, while they were almost absent among controls (1 of 70, p < 0.001 by χ(2) test). Vascular invasion and tumor budding were more frequent among Stage I patients with an unfavorable prognosis than in controls. By regression analyses, micrometastases (HR 12.3, CI 4.8-32) and vascular invasion (HR 3.5, CI 1.4-8.5) maintained an independent association with prognosis (cancer-specific survival). CONCLUSION: Micrometastasis in the lymph nodes can be revealed in the majority of patients with early colorectal cancer who die of tumor progression, while they appear extremely rare in Stage I individuals with good prognosis. The selection of patients through histology (vascular invasion) and search of occult metastatic cells might represent a way to identify individuals who might benefit from adjuvant chemotherapy.

Expression of the sodium/iodide symporter in human prostate adenocarcinoma.

OBJECTIVE: To analyze expression of the sodium/iodide symporter (NIS) in tissue specimen from a large series of patients with prostate adenocarcinoma. Few data are available on the NIS expression in prostate tumor tissues. METHODS: NIS protein expression was examined by immunohistochemistry in 78 tumor tissue specimen and their non-neoplastic counterparts. Total ribonucleic acid was extracted for semiquantitative reverse transcription polymerase chain reaction analysis of NIS transcript. The relationship between NIS expression and Gleason score, prostate-specific antigen levels and stage was also investigated. RESULTS: NIS protein was expressed in 41 of 78 prostate cancer (52.4%) and was located predominantly intracellularly, whereas immunoreactivity was missing in nontumor hyperplastic prostatic tissue. Absence of expression was mainly because of reduced or lost gene transcription, as detected by reverse transcription polymerase chain reaction. A statistically significant relationship was detected between presence of NIS expression and some markers of aggressiveness including stage > or =pT2a (P = .007) and Gleason score > or =8 (P = .014). CONCLUSIONS: Our data demonstrate the presence of NIS transcript and protein in about half of prostate cancer tissues and its relationship with clinical markers of aggressiveness. Thus, it may potentially serve as a biomarker for defining individuals with biologically active prostate cancer.

Prevalence and prognostic significance of microsatellite alterations in young patients with bladder cancer.

Mutations in microsatellite sequences are a hallmark of neoplastic transformation and have been reported in the majority of human cancers. Conflicting results have been reported on the role of microsatellite alterations in bladder tumorigenesis and it has been suggested that they might be mainly involved in the development of bladder cancers in young patients. In this study, DNA was extracted from laser-microdissected samples of 51 superficial papillary bladder urothelial carcinomas arising in young patients and was analyzed for the status of 19 microsatellite loci previously reported to be associated with bladder tumorigenesis. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with other clinicopathologic and molecular markers. The prognostic significance of these alterations was also evaluated. Loss of heterozygosity at one or more loci was detected in all 51 tumors analyzed. Length variation in at least one locus was observed in 48 (94%) of the cases. The microsatellite that was more frequently altered was D11S488 (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%), all the remaining being altered in less than 50% of cases. The occurrence of microsatellite alterations was not associated with tumor grade nor with tumor stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor p27Kip1 while it was significantly more frequent in tumors with increased expression of the proliferation marker MIB-1 (P=0.003). The occurrence of alterations at the analyzed loci was associated with a reduced risk of tumor recurrence (P=0.04 by log-rank test) and disease progression (P=0.02) in a univariate analysis. These findings demonstrate that microsatellite alterations are frequent and early events and might have a prognostic significance in bladder cancers arising at young age.

Does HPV play a role in the etiopathogenesis of ameloblastoma? An immunohistochemical, in situ hybridization and polymerase chain reaction study of 18 cases using laser capture microdissection.

Ameloblastomas are epithelial tumors of odontogenic origin, biologically characterized by local recurrence. Among different etiologic factors, HPV infection has been recently postulated to be somehow involved in ameloblastoma etiopathogenesis. To address this issue, we studied 18 ameloblastomas by means of immunohistochemistry, in situ hybridization (conventional and amplified), polymerase chain reaction and nested-polymerase chain reaction analyses using laser capture microdissection in order to detect the occurrence of HPV in this setting. No evidence of HPV infection was detected by morphological examination, immunohistochemistry, in situ hybridization and conventional polymerase chain reaction, while nested-polymerase chain reaction showed a weak positive band in two cases. However, the subsequent restriction enzyme analysis carried out from the nested-polymerase chain reaction amplification products of these two samples excluded the presence of HPV subtypes 16, 18, 31, 33, 35, 52, and 58. The search for HPV 6 and 11 in the same specimens was also negative. In conclusion, our data do not support an etiopathogenetic evidence for HPV in ameloblastoma.

Primary mixed adenocarcinoma and small cell carcinoma of the appendix: a clinicopathologic, immunohistochemical, and molecular study of a hitherto unreported tumor.

Appendiceal carcinoids range from well-differentiated endocrine tumor to well-differentiated endocrine carcinoma, while poorly differentiated (small cell) carcinoma has not been described in this site. We report herein a case of mixed intestinal-type adenocarcinoma associated with a small cell carcinoma arisen in a 35-year-old woman and clinically presenting as an appendiceal abscess. The resected tumor histologically appeared as a biphasic lesion composed of a nonmucinous adenocarcinoma closely juxtaposed with a poorly differentiated (small cell) endocrine carcinoma. The subsequent right hemicolectomy was unremarkable, but one pericolic lymph node showed a metastatic deposit consisting of the adenocarcinoma only. The patient thus underwent a chemotherapeutic protocol for colorectal cancer, and she is alive and well at the 65-month follow-up. Immunohistochemically, the adenocarcinoma strongly stained for cytokeratin 20 and carcinoembryonic antigen, while the endocrine component displayed a dot-like positivity for pan-cytokeratins and chromogranin. Of note, both components did not stain with CDX2 and p53. At genotypic analysis by microsatellite instability, both components shared many microsatellite alterations as well as a normal p53 gene setup, although small cell carcinoma harbored additional alterations. Clinical and molecular findings led us to consider this lesion as a clonal tumor in which the endocrine component seems to derive from a progressive differentiation of the adenocarcinoma following a glandular-to-endocrine sequence.

Superficial papillary urothelial carcinomas in young and elderly patients: a comparative study.

OBJECTIVE: To compare the clinicopathological and immunohistochemical findings of superficial papillary transitional cell carcinomas in "young" and "elderly" patients, as the natural history and prognosis of bladder tumours in young patients remains a matter of debate. PATIENTS AND METHODS: Tumours from 50 patients with superficial urothelial tumours of the bladder diagnosed before 45 years old ("young" group, follow-up 25-119 months) were compared with 90 similar tumours developed in patients aged >55 years ("elderly", follow-up 24-102 months). All the patients had a transurethral resection with curative intent, and none had received any therapy before surgery. After surgery only patients diagnosed with pT1 tumours were treated by intravesical bacille Calmette-Guérin (BCG) instillations; all received intravesical BCG if there was a recurrence. The clinicopathological variables, recurrence and disease-free interval to recurrence were assessed. Proliferative activity (MIB-1) and expression of cell-cycle regulation proteins cyclin D1, p53 and p27(kip1) were detected by immunohistochemistry in the tumours of both groups. RESULTS There were statistically significant differences in tumour grade, stage and occurrence between the "young" and "elderly" groups. The 'young' group had a longer disease-free interval to recurrence. Among the immunohistochemical markers analysed, only MIB-1 and cyclin D1 were associated with an increased risk of recurrence in the "young" group (P < 0.04 and <0.01, respectively) in a univariate analysis. CONCLUSIONS Superficial papillary urothelial tumours of the bladder in "young" patients had a better prognosis than those in the "elderly" group, showing a lower grade and stage at diagnosis, and a lower recurrence rate. Proliferative activity and cyclin D1 expression levels were of prognostic significance for the risk of recurrence in these patients.

Apoptosis in prostate carcinoma before and after neoadjuvant therapy with LH-RH analog.

This study investigated apoptosis in prostate cancer before and after neoadjuvant treatment with LH-RH analog, demonstrating that this therapy induced high AI and bax and survivin overexpression, thus acting as a proapoptotic agent in prostate cancer. A statistically significant correlation was found between high AI and overexpression of bax protein after therapy. It is probable that this kind of therapy is deeply implicated in promoting the apoptotic intrinsic pathway.

Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome.

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.