Effect of HCV NS_3 protein on P53 protein expression in hepatocarcinogenesis

AIM To investigate hepatocarcinogenesis by detecting the effect of HCV NS 3 protein on P53 protein expression in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue (PCLT). METHODS The expression of HCV NS 3 and P53 protein was detected with immunohistochemical technique (SP method) in specimens of HCC and PCLT from 47 patients with negative HBV. RESULTS The positive rate of HCV NS 3 protein was lower in HCC (62%) than in PCLT (83%) ( P <0 025). The better differentiaton of cancer cells, the stronger expression of HCV NS 3 protein ( P <0 025). The positive rate of P53 protein in HCC (81%) was higher than in PCLT (47%) ( P <0 025). The worse differentiaton of cancer cells, the stronger expression of P53 protein ( P <0 05). The P53 protein expression was not correlated with the HCV NS 3 protein expression in HCC ( P >0 5), whereas their expression was closely related to PCLT ( P <0 01), and the expression rate of P53 protein in the cases of positive HCV NS 3 protein was higher than that in the cases of negative HCV NS 3 protein. CONCLUSION HCV NS 3 protein may exert its hepatocarcinogenic effect in early stage on host cells by endogenous pathway which may bring about mutation of p53 gene and transformation of hepatocytes.

Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

Changes of p53 protein blood level in esophageal cancer patients and normal subjects from a high incidence area in Henan,China

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Effects of endotoxin on expression of ras, p53 and bcl-2 oncoprotein in hepatocarcinogenesis induced by thioacetamide in rats

AIM To evaluate the relationship between expression of ras, p53, bcl 2 gene products, and hepatocarcinogenesis since endotoxemia produced from lipopolysaccharide admi nistration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide. 〖WTH4〗METHODS〓〖WTXFZ〗The hepatocarcinoma model was induced by oral intake of 0 03% thioacetamide for six months. During the induction of hepatocarcinoma model, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied to quantitative analysis of the expression of oncogene proteins. RESULTS In this model system, overexpression of ras p21 protein mainly occurred on precancerous cell population or in early stage of hepatocyte transformation. And the levels of ras p21 declined when nuclear DNA aneuploid increased. Expression of bcl 2 protein slowly and steadily rose with more hepatocytes staying in S+G2M phases as the hepatocarcinoma became more malignant. P53 was moderately expressed during the hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes of ras, p53 and bcl 2 gene products. CONCLUSION Over expression of oncogene ras p21 was likely to be a precursor of the premalignant hepatocytes and it might be responsible for the initiation of hepatocarcinogenesis. Bcl 2 protein expression is proportional to the severity of the malignancies. P53 may be a key pathway on the transformation and development of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expressions of oncogene proteins reflected the properties of the premalignant and malignant cells, but not directly related to endotoxemia statistically.[JP]

Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma

AIM： To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein （PGP） and p53 protein in advanced hepatocellular carcinoma （HCC）. METHODS： The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug （epirubicin hydrochloride; anthracycline group）, and the remaining 21 were treated with a non-anthracycline drug （mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group）. The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS： Before the start of the treatment, PGPpositive rate was 90.2% （strongly-positive, 36.6%） and p53 protein-positive rate was 34.1% （strongly-positive, 19.5%）. In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression （P= 0.005）, and their prognoses were poor （P= 0.001）. in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients （P= 0.012）, irrespective of the survival outcome. CONCLUSION： The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

Clinical significance of immunohistochemica study of P53 protein in colorectal carcinoma

AIMS To determine the clinical significance of P53 protein ex-pression in colorectal carcinoma.METHODS The expression of P53 protein in 92 colorectal car-cinomas was examined using the monoclonal antibody PAb 1801.Correlation between P53 protein expression and prognosis in col-orectal carcinoma was analyzed using log-rank test.RESULTS The frequency of P53 protein expression was 57.61%,corresponding with Dukes’ staging.Analysis of survivordata demonstrated that the survival rate of colorectal carcinomawith positive P53 protein group was lower than that of negativeP53 protein group.CONCLUSIONS We conclude that the expression of P53 pro-tein is correlated with poor prognosis in colorectal carcinoma.

Relationship between ras p53 gene RNA and protein expression and HCC metastasis

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Prognostic values of apoptosis-stimulating P53-binding protein 1 and 2 and their relationships with clinical characteristics of esophageal squamous cell carcinoma patients:a retrospective study

Background: Esophageal squamous cell carcinoma(ESCC) is a leading cause of cancer?related death, and new prognostic biomarkers are urgently needed. Apoptosis?stimulating P53?binding protein 1(ASPP1) and 2(ASPP2) have been reported to play important roles in the development, progression, metastasis, and prognosis of cancers, but their roles in ESCC have not been elucidated. In this study, we examined the expression of ASPP1 and ASPP2 in ESCC to evaluate their prognostic values.Methods: The protein expression of ASPP1, ASPP2, and P53 in 175 specimens of ESCC was detected using immuno?histochemical staining; their expression in cancerous and noncancerous tissues was scored according to the stain?ing intensity and the percentage of stained cells. The associations of ASPP1, ASPP2, and P53 with clinicopathologic parameters, overall survival(OS), and disease?free survival(DFS) were analyzed.Results: The protein expression levels of ASPP2 and P53 were significantly higher in cancerous tissues than in paired noncancerous tissues(P < 0.001), whereas the expression levels of ASPP1 in the two groups were similar. In ESCCs, ASPP1 expression was significantly associated with histological differentiation(P = 0.002) and invasive depth(P = 0.014); ASPP2 expression was associated with age(P = 0.029) and histological differentiation(P < 0.001); and P53 expression was associated with age(P and P53 expression. Survival an= 0.021) and tumor size(P alysis revealed that high AS= 0.040). No correlations were found between ASPP1, ASPP2,PP2 expression was significantly associated with increased 5?year OS(P = 0.001) and DFS rates(P ate of ESCC patients(= 0.010) and that high P53 expression was significantly associated with a reduced 5?year DFS rP atio(HR): 0.541, 9= 0.015). Multivariate Cox analysis indicated that ASPP2 was an inde?pendent predictor of OS [hazard r5% confidence interval(CI) 0.363–0.804] and DFS(HR: 0.599, 95% CI 0.404–0.888) of ESCC patients and that P53 was an independent predictor of DFS(HR: 2.161, 95% CI 1.100–4.245).Conclusions: ASPP1 might be involved in the progression of ESCC, and ASPP2 was a potential prognostic biomarker of ESCC and should be evaluated in future studies.

Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer

AIM： Overexpression of tumor protein p53-induced nudear protein 1 （TP53INP1） induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer, METHODS： TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed. RESULTS： TP53INP1 was expressed in 98% （139/142 cases） of non-cancerous gastric tissues and was downexpressed in 64% （91/142 cases） of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased （43.9%） in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma （81.6%）. Cancers invading the submucosa or deeper showed lower positively （59.1%） compared with mucosal cancers （85.2%）. Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion （54.3% vs 82.0% without lymphatic invasion） and node-positive patients （31.3% vs 68.3% in node-negative patients）. P53 was expressed in 68 （47.9%） patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells： the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP41-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis （P= 0.0006）.CONCLUSION： TPS3INP1-positive rate decreases with the progression of gastric cancer. TPS3INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TPS3INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TPS3INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.

AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability

The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function.

Role of microRNA-21 in uveal melanoma cell invasion and metastasis by regulating p53 and its downstream protein

AIM： To reveal the insight mechanism of liver metastasis in uveal melanoma, we investigated cell functions of microRNA-21 in three different uveal melanoma cell lines and analyze the relationship of target gene p53 and its downstream targets which been found significant expression in our previous study.METHODS： Quantitative real-time polymerase chain reaction （qRT-PCR） was used to detect microRNA-21 expression in normal uveal tissue and uveal melanoma cell lines. Lenti-virus expression system was used to construct OCM-1, MuM-2B and M619 cell line with stable overexpression and inhibition of microRNA-21. In vitro cell function tests such as cell proliferation, cell apoptosis, cell circle and abilities of migration and invasion were examined by MTT, BrdU assay, flow cytometry, transwell assay and Matrigel invasion assay respectively. The target gene was predicted by bioinformatics and confirmed by using a dual luciferase reporter assay. The expression of p53 and its suspected downstream targets LIM and SH3 protein 1 （LASP1） and Glutathione S Transferase pi （GST-Pi） were determined by qRT-PCR in mRNA level and western blotting analysis in protein level. Finally, the effect of microRNA-21 in a xenograft tumor model was assessed in four-week-old BALB/c nude mice. RESULTS： Compared to normal uveal melanoma, expressions of microRNA-21 were significantly higher in uveal melanoma cell lines. Overexpression of microRNA-21 promoted proliferation, migration, and invasion of OCM-1, M619 and MuM-2B cells, while inhibition of microRNA-21 reveal opposite effects. Wild type p53 was identified as a target gene of microRNA-21-3p, and proved by dual luciferase reporter assay. Up-regulated microRNA-21 inhibited the expression of wild type p53 gene, and the increased expression of LASP1 in mRNA level and protein level, while down-regulated microRNA-21 presented opposite way. However, GST-pi showed the potential pattern as expected, but relative mRNA level showed no statistically significant difference in OCM-1 cells. Furthermore, the mRNA expression of GST-pi was decreased in microRNA-21 overexpressing MuM-2B, and increased in M619 cells with inhibition of microRNA-21. In vivo, inhibition of microRNA-21 reduced tumor growth with statistically significant difference.CONCLUSION： These findings provide novel insight into molecular etiology of microRNA-21 in uveal melanoma cell lines, and suggest that microRNA-21 might be a potential candidate for the diagnosis and prognostic factor of human uveal melanoma in future.

DNA PLOIDY，EXPRESSION OF p53 PROTEIN AND METASTATIC BEHAVIOUR OF GASTRIC CARCINOMA

DNA ploidy of 57 gastric carcinomas with metastases(12 liver,1 adrenal,4 ovary and 48 lymph node) were measured by flow cytometry.DNA anueploidy was significantly related to liver metastases:9 out of 12 gastric carcinomas with liver metastases were anueploid(75%) as compared to 13 out of 45(28.8%) of cases without liver metastases(P<0.01);the one gastric carcinoma with adrenal metastasis was also anueploid.DNA ploidy was not related to ovarian or lymph node metastases.Another interesting finding was that all of 3 gastric carcinomas with liver metastases which showed a diploid DNA pattern,expressed p53 protein, while all of 3 carcinomas with liver metastases but no p53 protein expression were anueploid.The expression of p53 protein was not related to ovarian metastases.The results suggested that an anueploid DNA pattern and the expression of p53 protein are both objective markers valuable in predicting high risk potential of metastases to the liver,and that the combined detection of these markers can be a most useful method in the follow-up of Patients with gastric carcinoma in detecting those at high risk of developing metastases following surgical resection.Also the poorer prognosis of Patients with gastric carcinoma showing an anueploid DNA pattern may be related to the development of distant organ metastases through the blood vascular system.Furthermore,the clone of gastric carcinoma cells which accumulate p53protein or show an anueploid DNA pattern may have a causative role in the development of liver(&.adrenal) metastases.

Killing of p53-deficient hepatoma cells by parvovirus H-1 and chemotherapeutics requires promyelocytic leukemia protein

AIM: To evaluate the synergistic targeting and killing of human hepatocellular carcinoma (HCC) cells lacking p53 by the oncolytic autonomous parvovirus (PV) H-1 and chemotherapeutic agents and its dependence on functional promyelocytic leukemia protein (PML). METHODS: The role of p53 and PML in regulating cy-totoxicity and gene transfer mediated by wild-type (wt) PV H-1 were explored in two pairs of isogenic human hepatoma cell lines with different p53 status. Further-more,H-1 PV infection was combined with cytostatic drug treatment. RESULTS: While the HCC cells with different p53 status studied were all susceptible to H-1 PV-induced apoptosis,the cytotoxicity of H-1 PV was morepronounced in p53-negative than in p53-positive cells. Apoptosis rates in p53-negative cell lines treated by genotoxic drugs were further enhanced by a treatment with H-1 PV. In flow cytometric analyses,H-1 PV infection resulted in a reduction of the mitochondrial transmembrane potential. In addition,H-1 PV cells showed a significant increase in PML expression. Knocking down PML expression resulted in a striking reduction of the level of H-1 PV infected tumor cell death. CONCLUSION: H-1 PV is a suitable agent to circumvent the resistance of p53-negative HCC cells to genotoxic agents,and it enhances the apoptotic process which is dependent on functional PML. Thus,H-1 PV and its oncolytic vector derivatives may be considered as therapeutic options for HCC,particularly for p53-negative tumors.

Effect of Electroacupuncture on Expression of p53 Protein in Cerebral Cortex of Rats with Global Cerebral Ischemia/Reperfusion Injury

Objective: To observe the effect of electroacupuncture (EA) on expression of p53 protein in cerebral cortex of senile rats with global cerebral ischemia/reperfusion (IR) injury and to explore its mechanism. Methods: The cerebral IR injury rat model was established referring to Pulsinelli 4-vessel occlusion method. Thirty-six SD rats were randomly and evenly divided into the control group, the IR group and the IR plus EA (IR-EA) group. The animals in the control group were subjected to electrocauterization of vertebral arteries in bilateral flank orifice alone with the general carotid arteries unoccluded. To rats in the IR-EA group, immediately and 24h, 48h, 72h after cerebral IR, EA treatment on bilateral acupoint 'Zusanli' (ST36) was applied once a day, lasting for 60 minutes. After the final treatment, all the rats were sacrificed and their brains were taken to examine p53 protein expression by the immunohistochemical method. Results: Cells with positive p53 immunoreactivity in the cerebral cortex of rats in the IR group was significantly higher than that in the control group ( P<0. 05), while that in the IR-EA group was significantly lower than that in the IR group ( P<0. 05). Conclusion: EA could remarkably reduce expression of p53 protein in the cerebral cortex of senile rats with global cerebral IR injury, which might be one of the means for EA to inhibit neuronal ap-optosis after cerebral IR injury.

PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

EXPRESSION OF P53 PROTEIN AND PROLIFERATING CELL NUCLEAR ANTIGEN IN HUMAN GESTATION TROPHOBLASTIC DISEASE

To study the relationship between p53 protein, proliferating cell nuclear antigen (PCNA) expression and benign or malignant gestational trophoblastic disease (MGTD). Methods: The histotomic sections of 48 patients with gestational trophoblastic disease and 24 patients of normal chorionic villi were stained using immunohistochemistry. The monoclonal antibodies were used to determine p53 protein and PCNA. Results: The frequency of p53 and PCNA positive expression were significantly different among the chorionic villi of normal pregnancy, hydratidiform mole (HM) and MGTD. But neither p53 nor PCNA has any relation with the clinical staging or metastasis of MGTD. Conclusion: Both P53 and PCNA are valuable in diagnosis of human gestational trophoblastic disease.

Correlation and Expression of COX-2 and P53 Protein in Basal Cell Carcinoma of Eyelid

The correlation between the expression of COX-2 and p53 protein in basal cell carcinoma （BCC） of eyelid and apoptosis was investigated. Specimens of BCC were collected from 40 cases （aged 28-68 y） at the Department of Pathology, Renmin Hospital of Wuhan University, and Department of Pathology, Zhongnan Hospital of Wuhan University during from 1999 to 2006. Five specimens of paracancerous tissues served as control group. Immunohistochemical staining was performed to detect the expression of COX-2 and p53 in the tissues. The average absorbance （A） and the average positive area rate of COX-2 and p53 protein were measured by image analysis. The positive area rate of COX-2 and p53 protein was analyzed by linear correlation analysis. It was found that COX-2 and p53 proteins were highly expressed in BCC of eyelid, and weakly expressed in paracancerous tissues. Image analysis revealed that the expression of COX-2 and p53 proteins in BCC of eyelid was sig- nificantly higher than that in paracancerous tissues （P〈0.01）. Spearman rank correlation analysis demonstrated a positive correlation between the expression of COX-2 and p53 （r=0.113, P=0.421）. It was concluded that COX-2 can increase the expression of p53 protein, therefore suppressing apoptosis.

Study on the correlation between CT appearance and expression of p53 protein in peripheral lung cancer

Objective: To investigatethecorrelationbetweenCT appearanceandexpressionof p53proteininperipheral lungcancer.Methods:Theexpressionof p53proteinwasexaminedby meansof SP immunohistochemicaltechniquein32casesof peripherallungcancer.TheircorrelationwiththepreoperativeCT appearancewas analyzedretrospectively.Results:Theexpressionof p53proteinwascorrelatedwithtumorsize,lobulation,cavitation,pleuralindentationandme-diastinallymphnodeenlargement,butnotwithspiculation.Tumorwithmaximumdiametergreaterthan3cm or withthe presenceof lobulation,cavitation,pleuralindentationor mediastinallymphnodelarger than10mminshortaxishada rel-ativelyhigherlevelof p53expression.Conclusion:CT signsof peripheral lungcancersarevaluablenotonlyindifferen-tiatingcancersfrombenignlesions,as knownbefore,butalsoinprovidingfurtherinformationforthemalignantpotential of cancers.Largertumorsize,lobulation,cavitation,pleuralindentation,andmediastinallymphnodeenlargementmaybe likelyrelatedto a higherdegreeof malignantpotentialandmoreaggressivetumorbehavior.

Orthopedic manifestations of Li-Fraumeni syndrome:Prevention and treatment of a polymorphic spectrum of malignancies

Li-Fraumeni syndrome(LFS)is a rare hereditary cancer predisposition syndrome characterized by a heightened risk of developing various malignancies at an early age.Emerging evidence suggests a correlation between LFS and orthopedic manifestations,underscoring the importance of orthopedic screening in individuals with this syndrome.Pediatric cancer is rare.It is estimated that more than 10%-15%of tumors are secondary to a pathogenic variant in a cancer predisposition gene.More than 100 cancer predisposition genes and their association with syndromes or isolated tumors have been identified.LFS is one of those who have been most widely described.Patients with this syndrome present a high risk of developing one or more tumors.Its knowledge enables the establishment of a follow-up protocol for the patient and affected family members,facilitating early detection of new tumors and reducing tumor and treatment-related morbidity and mortality.The primary objective of this invited editorial article is to provide a thorough review of the existing knowledge of LFS and its polymorphic spectrum of related malignancies,with a focus on aspects directly linked to orthopedic manifestations.Another objective is to offer an update on the most modern prevention,treatment and follow up guidelines that could be useful for the physicians dealing with this cohort of patients.