We have reported that mesenchymal stromal/stem cells (MSCs) deficient for p53 alone or together with RB (p53(-/-)RB(-/-)) originate leiomyosarcoma after subcutaneous (s.c.) inoculation.
The p53 and phosphoinositide-3-kinase, catalytic, alpha polypeptide/v-akt murine thymoma viral oncogene homolog/mechanistic target of rapamycin (PIK3CA/AKT/mTOR) pathways frequently are altered in sarcoma with complex genomics, such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS).
Conversely, p53 null mutations (frameshift, splice sites, nonsense) and mutations outside the DNA-binding domain were associated with leiomyosarcoma (OR, 10.1; 95% CI, 3.4-29.9), a type of sarcoma that occurred after age 20 years.
These results suggest that the loss of RB and P53 may have contributed to the initiation and/or progression of the leiomyosarcoma of the bladder in this patient.
Our results indicate that p53 abnormalities are major events and that an increasing level of p53 mRNA is associated with an overexpression of p53 protein in leiomyosarcoma and they may play an important role in the tumorigenesis in this tumor.
Restoration of wt p53 expression in human leiomyosarcoma SKLMS-1 cells that contain mutant p53 markedly inhibited angiogenesis induced by tumor cells in vivo.
According to our results, p53 protein nuclear expression was detected in 20% (8/40) of the tumours (1 fibrosarcoma, 2 liposarcomas, 1 leiomyosarcoma, 1 rhabdomyosarcoma, 2 Ewing's sarcomas and 1 unclassified sarcoma).
In this study, we analyzed cell proliferating factors (mitotic and Ki-67 indices) and the p53 status of both types of leiomyosarcoma (37 cases) to evaluate the possibility that these factors may serve as indicators in prognosis.
It was suggested that P53 over-expression might be associated with the transformation of leiomyoma into leiomyosarcoma and could be used as an objective parameter in distinguishing the malignant from the benign and predicting the prognosis of patients with smooth muscle tumors of the gastrointestinal tract.
Notably, the splicing events of certain STS key genes were significantly associated with STS 2-year overall survival in the present study, including exon skip (ES) events in MDM2 and EWSR1, alternate terminator events in CDKN2A and HMGA2 for dedifferentiated liposarcoma, ES in MDM2 and alternate promoter events in CDKN2A for leiomyosarcoma, and ES in EWSR1 for undifferentiated pleomorphic sarcoma.
Compared with leiomyoma (LM), the figures for the strength of association were as follows: LM variants (RR = 1.53, 95%CI = 1.03-2.27, P = 0.036, random effect); leiomyosarcoma (LMS) (RR = 3.20, 95%CI = 1.68-6.12, P < 0.001, random effect); and smooth muscle tumors of uncertain malignant potential (STUMP) (RR = 2.90, 95%CI = 1.17-7.21, P = 0.022, random effect). p16INK4a expression was significantly higher in LMS than in LM variants (RR = 3.74, 95%CI = 1.96-7.13, P < 0.001, random effect) or STUMP (RR = 1.67, 95%CI = 1.26-2.23, P < 0.001, fixed effect).
We investigated p16 expression in leiomyomas with infarct-type necrosis, tumours which may sometimes be misinterpreted as smooth muscle tumours of uncertain malignant potential or even leiomyosarcoma on conventional light microscopy.
Thus, we investigated the expression of members of the VEGF receptor (VEGFR) family and corresponding growth factors in leiomyosarcoma tissue specimens and in the leiomyosarcoma cell lines SK-LMS-1 and SK-UT-1.
On protein level, expression of p16(INK4a) was observed in undifferentiated pleomorphic sarcoma (UPS) in 69.1%, leiomyosarcoma in 85.7%, synovial sarcoma in 77.8%, liposarcoma in 88.9%, angiosarcoma in 60.9% and MPNST in 22.2%.
We highlight the difficulty in distinguishing tumour cell necrosis from infarct-type necrosis and the limited utility of p16 immunohistochemical expression in the diagnosis of leiomyosarcoma.
Knockdown of Slug expression in SK-LMS-1 leiomyosarcoma cells by siRNA significantly increased E-cadherin; decreased the mesenchymal markers vimentin and N-cadherin (encoded by CDH2); and significantly decreased cell proliferation, invasion, and migration.
To investigate the potential role of p16 in soft tissue leiomyosarcoma (LMS), an immunohistochemical analysis was performed of 77 LMSs for p16 expression.
For in vivo studies, 10 animals harboring SK-LMS-1 human leiomyosarcoma cells were randomly divided and treated twice on days 0 and 9 intraneoplastically with either 1 x 10(7) plaque-forming units of d12.CALP/100 mm(3) of tumor volume or with medium alone.
A plasmid containing a human calponin h1 complementary DNA and a bacterial neomycin-resistance gene was transfected into the human leiomyosarcoma cell lines SKN and SK-LMS-1 by electroporation.