Intestinal neurofibromatosis and small-bowel adenocarcinoma: a single case study.

OBJECTIVE: Patients with Von Recklinghausen's disease (neurofibromatosis type 1) are at increased risk of developing various tumours. However, the coexistence of neurofibromatosis with small-bowel adenocarcinoma is exceedingly rare. We present an uncommon case of neurofibromatosis type 1, involving the small bowel in a 73-year-old man, who was admitted to our department with signs of acute abdomen. At laparotomy, multiple mesenteric and intramural nodules were seen in the distal ileum. These nodules obstructed ileal lumen, while the intestine wall was perforated in one point. A wide resection of the affected ileum together with all visible nodules in the adjacent mesentery was performed. Histology revealed neurofibromatosis type 1 with malignant transformation to small-bowel adenocarcinoma. The patient had no additional therapy. In a follow-up of 2 years, the patient is very well and there was no recurrence of the disease. We suggest that adenocarcinoma of small bowel should be considered in the evaluation of acute abdominal pain in neurofibromatosis patients.

Immunohistochemical expression of p53, p21/waf1, rb, p16, cyclin D1, p27, Ki67, cyclin A, cyclin B1, bcl2, bax and bak proteins and apoptotic index in normal thymus.

The immunohistochemical expression of p53, p21, Rb, p16, cyclin D1, Ki67, cyclin A, cyclin B1, p27, bcl2, bax, and bak proteins and the apoptotic index (Al) were investigated in 20 normal thymuses (8 adults, 3 adolescents, 5 infants and 4 newborns). The expressions of Rb, Ki67, cyclin A and cyclin B1 were overlapping, being high in the cortex with a tendency for decreased expression toward the medulla. Apoptotic cells were mainly detected in the cortex and the corticomedullary junction, rarely being present in Hassall's corpuscles. The mean values of Ki67, cyclin A, and cyclin B1 expression in thymuses were 77.2%, 32.2% and 21.4% (newborns), 62.4%, 33.7% and 18.5% (infants), 56.9%, 23.4% and 18.9% (adolescents) and 38.7%, 21.7% and 14.6% (adults), respectively. The mean values of AI in thymuses from newborns, infants, adolescents and adults were 1.4%, 2.9%, 2.7% and 3.8%, respectively. This decrease in proliferation and increase in apoptosis may account for the process of thymic involution. P16 expression was widespread with most of Hassall's corpuscles being p16-positive. P16-positive cells and Hassall's corpuscles increased with the increase in age, in keeping with the suggested role of p16 in cellular senescence. P27 expression was undetectable in subcapsular thymocytes with a tendency for increased expression toward the medulla. The expressions of Ki67, cyclin A and cyclin B1 were inversly related with that of p27, consistent with previous evidence that p27 concentration is reduced when the cell-cycle progresses. P21 and much less frequently p53 proteins were mainly detected in a part of the subcapsular cortical epithelial cells. These findings suggest that a) in thymocytes, the apoptotic pathway is mostly p53-independent and the function of p21 as a negative regulator of the cell cycle must be redundant to other negative regulators, such as p16 and p27 which were abundantly detected in thymocytes and b) in some thymic epithelial cells, the p21 expression may be induced by p53, but in most of them seems to be p53-independent. Most of Hassall's corpuscles were p21-positive, consistent with previous evidence that these structures represent end stages of maturation of thymic medullary epithelium and that p21 protein is involved in the process of terminal differentiation. Cyclin D1 positivity was found in some macrophages. Bcl2 expression was mainly seen in medullary thymocytes, reflecting the surviving thymocytes in this region. The expressions of Bax and bak were more widespread in both the medulla and cortex, suggesting that these proteins play a broader role than bcl2 in the regulation of thymic apoptosis.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2. P53 and the wild-type (wt) p53-induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 does not maintain its suppressive effect on bcl-2 expression as has been reported in vitro. Further studies at the DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and wafl genes in SCLC pathogenesis.

Immunohistochemical detection of bcl2, p53, mdm2 and p21/waf1 proteins in small-cell lung carcinomas.

Thirty-one cases of small cell lung carcinomas (SCLC) were investigated by immunohistochemistry for the expression of bcl-2, p53 and the wild-type (wt) p53- induced proteins mdm2 and p21/waf1. Bcl-2 protein was detected in 24/31 cases of SCLC(77%) and p53 protein in 13/31 cases (42%). No correlation was found between histological subtype of SCLC and bcl-2 or p53 expression. Comparison between bcl-2 and p53 expression showed that 14/31 cases (45%) were only bcl-2 positive, 3/31 (11%) were only p53 positive, 10/31 (32%) were positive for both proteins and 4/31 (13%) were negative for both proteins. Mdm2 protein was detected in 2/32 SCLC which were also p53 positive. P21 protein was detected in 6/32 SCLC. Four of the p21 positive SCLC were negative for both p53 and mdm2, and two were positive for both p53 and mdm2 proteins. The significant expression of bcl-2 protein in SCLC suggests that bcl-2 may be involved in the pathogenesis of most SCLC by inhibiting apoptosis during neoplastic transformation. The expression of p53 protein in SCLC is likely to be related to underlying p53 gene mutations since these genetic alterations are very frequent in SCLC. This can be supported by our findings that 11/13 p53 positive SCLC were mdm2 and p21 negative. The two cases with p53+/mdm2+/p21+ phenotype may represent tumours with wt p53 gene and p53 protein immunoexpression due to binding to mdm2 protein. The four cases with p53-/mdm2-/p21+ phenotype may represent tumours with p53-independent p21 protein expression. Coexpression of p53 and bcl-2 proteins in a proportion of SCLC suggests that in these tumours p53 doses not maintain its suppressive effect on bcl-2 expression as it has been reported in vitro. Further studies at DNA and RNA level are required to clarify the involvement of bcl-2, p53, mdm2 and waf1 genes in SCLC pathogenesis.