Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.

Posttransplant CD30+ anaplastic large cell lymphoma with skin and lymph node involvement.

Posttransplant (i.e. status with the transplant present) lymphoproliferative disorders (PTLD) are common conditions in transplant recipients. Most examples are of B cell origin, and CD30+ T cell PTLD are very rare. We report a CD30+ anaplastic large cell lymphoma (ALCL) in the skin of the right lower leg and in draining lymph nodes of the right inguinal region in an immunosuppressed 59-year-old male who had received a renal graft 9 years previously. Unlike the vast majority of PTLD, an incomplete T cell immunophenotype was observed, and there was evidence of T cell lineage at the genetic level reflected by a rearranged T cell receptor gamma gene. The neoplastic cells were non-reactive to the anaplastic lymphoma kinase (ALK) 1 protein. In addition, Epstein-Barr virus and human herpesvirus 8 sequences were absent. Arguments against a primary cutaneous ALCL, which is also ALK-1 negative, include systemic presentation at the time of initial diagnosis and immunoreactivity of the neoplastic cells to epithelial membrane antigen. Typically, our rare example of a posttransplantation systemic ALCL showed an aggressive behaviour and a poor response to both chemotherapy and local irradiation.

[Cystic lymphangioma of the transverse mesocolon]. / Cystisches Lymphangiom im Mesocolon transversum.

Intraabdominal cystic lymphangiomas are very rare. One new case of the disease is presented here: a 10-year-old boy undergoes laparotomy because of suspected appendicitis acuta, a cystic tumor in the transverse mesocolon is found and a segmental colon resection with primary anastomosis performed. Histologic examination of the tumor leads to the diagnosis of cystic lymphangioma. The postoperative course is uneventful. History, clinical features, diagnosis, therapy and pathologic-anatomical findings are discussed and the literature is reviewed.

[Microangiopathic hemolytic anemia, erythrophagocytosis and consumption coagulopathy in vinyl chloride-induced hemangiosarcoma of the spleen and liver]. / Mikroangiopathische hämolytische Anämie, Erythrophagozytose und Verbrauchskoagulopathie bei vinylchloridinduziertem Hämangiosarkom von Milz und Leber.

A case of angiosarcoma of the liver and the spleen following vinyl chloride exposure is described. The main symptoms in clinical diagnosis were microangiopathic hemolysis, disseminated intravascular coagulation, hepatosplenomegaly and exposure to vinyl chloride thirty years ago. It is the first case in which liver and spleen are involved in angiosarcoma due to vinyl chloride exposure. The tumor cells showed angioformative and solid histiocytoid growth with erythrophagocytosis.