primary brain tumors account for 2% of human neoplasms in adults and for 20% in pediatric patients . these tumors consist of a varied group of neoplasms which arise in the brain and its surrounding structures . the word health organization ( who ) established a uniform terminology and grading system for brain tumors . neuroepithelial tumors , the most prevalent group , include glioblastoma multiforme ( gbm ) , medulloblastoma and astrocytoma , while tumors of the meninges include meningioma . pylocitic astrocytoma ( grade i ) usually occurs in children or young adults , while astocytomas of other grades are typically diagnosed in adults . gbm is the most common and deadliest malignant primary brain tumor in adults , classified as grade iv astrocytoma . medulloblastoma is the most common embryonal tumor ( these are tumors that arise from embryonal or immature cells at the earliest stage of their development ) ; it occurs in children and young adults . meningiomas are tumors of meningothelial cells ; they appear in childhood or adolescence , but most are diagnosed in middle or later adult life . atypical meningiomas ( grade ii ) show more cellularity , mitotic activity and foci of necrosis than grade i meningiomas . heat shock proteins ( hsps ) are a class of molecules highly conserved during evolution with crucial roles in tissue homeostasis . due to their importance for cell survival and function , it has been postulated that they may be involved in the development of a number of human diseases , now called chaperonopathies . some forms of tumors are now considered chaperonopathies by collaboration , since chaperones favor the tumor ( e.g. , by inhibiting tumor cell apoptosis and/or antitumor immune response ) rather than the host organism . the presence and levels of various hsps in human brain tumors have not been extensively investigated to date . we conducted a study on a subset of human brain neoplasms to compare the levels of two hsps considered among the most important players during carcinogenesis . sixty brain tumors , including both neuroepithelial and meningeal neoplasms , classified accordingly to the who parameters , were retrospectively collected from files of the pathologic anatomy unit of the civico hospital , palermo , italy . in particular , we randomly selected ten pilocytic astrocytomas [ female : male ( f : m ) ratio = 1:4 ; age range : 4 - 17 yrs ] , ten grade ii astrocytomas ( f : m ratio = 1:1 ; age range : 27 - 84 yrs ) , ten glioblastoma multiformae ( f : m ratio = 4:1 ; age range : 44 - 73 yrs ) , ten medulloblastomas ( f : m ratio = 2:3 ; age range : 8 - 23 yrs ) , ten grade i meningiomas ( f : m ratio = 4:1 ; age range : 41 - 76 yrs ) , and ten grade ii meningiomas ( f : m ratio = 1:1 ; age range : 59 - 77 yrs ) . moreover , we selected five normal brain samples ( f : m ratio = 1:1 ; age range : 4 - 85 yrs ) from our files , and obtained slides showing normal glial cells , neurons and meningeal ( pial ) cells to be used as normal controls . we obtained sections of a thickness of 4 - 5 m from all specimens for histological re - evaluation and immunohistochemical testing . the primary antibodies used were anti - hsp60 ( mouse monoclonal antibody , dilution 1:400 , cat . h4149 , sigma co. , saint louis , mo , usa ) , and anti - hsp70 ( mouse monoclonal antibody , dilution 1:200 , cat . appropriate positive controls , as well as non - immune serum for negative controls , were run concurrently . immunostaining evaluations were performed by two blinded expert pathologists ( fr , ns ) and the percentage of positive tumor cells was calculated in ten random high power fields at a magnification of 400x . briefly , we used the mann - whitney u - test for comparison between groups and the kruskal - wallis test for multiple comparisons . statistical analyses of the immunohistochemical experiments showed that hsp60 levels were significantly higher p<0.01 ) than those of hsp70 in neuroepithelial tumors ( figure 1 ) , while levels of both molecules did not show any significant difference from each other in meningeal neoplasms ( p>0.05 ) . in particular , hsp60 immunopositivity was present mainly at the cytoplasmic level , while hsp70 immunopositivity was found both in the cytoplasm and nucleus of tumor cells ( figures 2 and 3 ) . the levels of these molecules in the normal control cells were always very low ( figures 2 and 3 , insets ) . finally , the levels of hsp60 and hsp70 did not correlate with the different types ( who grade ) of neoplasm ( data not shown ) . our results are partially in agreement with previous studies ; in particular , kato and colleagues found hsp60 immunopositivity in a number of brain tumors , while no significant immunohistochemical reactions were seen in sections of normal brain tissue . found hsp70 presence in glial tumors , mainly in the cytosol , and described a statistically significant association of the cytosolic hsp70 expression with a nuclear expression of the bcl2-associated athano - gene 1 ( bag1 ) protein . finally , hauser et al . described hsp70 , hsp27 and hsp90 positivity in medulloblastomas , with no association with tumor prognosis , indicating these proteins as a putative molecular target for anticancer therapy . hsp60 is classically considered a mitochondrial molecule , while hsp70 is commonly present in the cytosol . the presence of a diffuse immunohistochemical positivity for hsp60 in the cytoplasm , as well as a nuclear positivity for hsp70 , have already been described in other forms of solid tumors and have been correlated with tumor progression . the significant difference between hsp60 and hsp70 levels specific to neuroepithelial tumors may suggest that the former is not increased by a passive phenomenon ( e.g. , due to the stress caused by the peritumor environment on cancer cells ) but it may instead be actively implicated in tumor progression , e.g. by inhibiting tumor cell death or favoring tumor progression by inhibiting the antitumor response of the immune system , as already postulated in vitro . , moreover , these data confirm that hsp60 may have different levels and expression than hsp70 in different neoplasms , including head and neck cancer , salivary gland tumors and esophageal adenocarcinomas . however , its participation in meningeal tumor pathogenesis needs to be further investigated also with the use other techniques like proteomics . indeed , various studies using different techniques have found hsp60 expression to be increased , decreased or unchanged in several tumors of different anatomical districts . furthermore , an increase in hsp60 expression may correlate either with a more favorable or a worse prognosis . from a molecular point of view , when increased hsp60 accumulate in the cytosol where it may have either a pro- or an anti - apoptotic action , depending on whether it has been released by mitochondria or accumulated in the cytosol without mitochondrial import , respectively . for these reasons , hsp60 has been proposed as the molecular proteus of carcinogenesis . in addition , when accumulated in the cytosol , hsp60 may transfer to the plasma membrane of tumor cells , in turn becoming internalized by lipid rafts in multivesicular bodies and secreted by exosomes . finally , some anticancer drugs cause the release of exosomes loaded with hsp60 , which elicit effective natural killer cell antitumor responses , in vitro . in our opinion , we are not far from fully understanding the mechanisms by which hsp60 participates in tumor progression . molecular studies concerning post - translational modifications that cytosolic hsp60 undergoes when accumulating in the cytosol of tumor cells could help to fully characterize this proteiform molecule .
in this work we analysed , by immunohistochemistry , a series of brain tumors to detect the levels and cellular distribution of hsp60 and hsp70 . 
 we found that hsp60 levels were significantly higher than those of hsp70 in neuroepithelial tumors , while levels of both molecules were not significantly different from each other in meningeal neoplasms . 
 in particular , hsp60 immunopositivity was present mainly at the cytoplasmic level , while hsp70 immunopositivity was found both in the cytoplasm and in the nucleus of tumor cells . 
 the levels of these molecules in healthy control cells were always very low . 
 finally , hsp60 and hsp70 levels did not correlate with the different types ( who grade ) of neoplasm . 
 our results are partially in agreement with previous studies and suggest that hsp60 is not increased by a passive phenomenon ( e.g. , due to the stress caused by the peritumor environment on cancer cells ) but may be actively implicated in tumor progression , e.g. inhibiting tumor cell death or antitumor immune system response , as already postulated in vitro . 
 we also briefly discuss the most recent publications on the extramitochondrial localization of hsp60 in tumor cells and its role in tumor progression .