Role of polyphenols and nonpolyphenols against toxicity induced by fluoride: a comprehensive review.

Since its discovery as an antimicrobial agent, fluoride has been used in the control of dental caries. Many studies have shown that the chronic exposure of fluoride in high concentrations causes adverse effects in multiple organs; the use of bioactive compounds present in foods as a tool to mitigate the effects of fluoride could potentially be useful for populations in different parts of the world are exposed to fluoride in a chronic and systemic way. Thus, the aim of this comprehensive review is to present and discuss the published papers that focused on the use of polyphenols and nonpolyphenols that can mitigate the harmful activities promoted by fluoride exposure. Certainly, these data will contribute toward a better understanding of the role of food compounds in the pathological outcomes induced by fluoride. The new information will be added to that already available for regulatory purposes as a safe way to promote oral healthcare and prevent oral carcinogenesis.

Grade I meningiomas with atypical characteristics: a worse prognosis.

OBJECTIVE: The study reviewed the histology of cases of grade I meningiomas with spontaneous necrosis, grade I without necrosis and grade II meningiomas, to evaluate the histological and immunohistochemical factors of the patients' prognosis, while correlating the clinicopathological features with the clinical follow-up of the patients. METHODS: A review of 47 cases from the Department of Pathology of UNIFESP was performed and the samples were submitted to immunohistochemical examination with the p53 protein, Ki-67 cell proliferation factor and progesterone receptor markers. RESULTS: A greater expression was found in the progression of several degrees of aggressiveness for p53 and Ki-67, and a higher frequency of progesterone receptors in the lower degrees. CONCLUSIONS: The group of grade I meningiomas with spontaneous necrosis showed histological and immunohistochemical indexes that approximate those of the grade II meningioma. This suggests a worse prognosis for grade I meningiomas with necrosis.

Grade I meningiomas with atypical characteristics: a worse prognosis / Meningiomas grau I com características atípicas: um pior prognóstico

ABSTRACT The study reviewed the histology of cases of grade I meningiomas with spontaneous necrosis, grade I without necrosis and grade II meningiomas, to evaluate the histological and immunohistochemical factors of the patients' prognosis, while correlating the clinicopathological features with the clinical follow-up of the patients. A review of 47 cases from the Department of Pathology of UNIFESP was performed and the samples were submitted to immunohistochemical examination with the p53 protein, Ki-67 cell proliferation factor and progesterone receptor markers. A greater expression was found in the progression of several degrees of aggressiveness for p53 and Ki-67, and a higher frequency of progesterone receptors in the lower degrees. The group of grade I meningiomas with spontaneous necrosis showed histological and immunohistochemical indexes that approximate those of the grade II meningioma. This suggests a worse prognosis for grade I meningiomas with necrosis.

RESUMO O objetivo do estudo foi realizar a revisão histológica de casos de meningiomas grau I com necrose espontânea, grau I sem necrose e grau II para avaliar os fatores histológicos e imunohistoquímicos de prognóstico dos pacientes, correlacionando informações no âmbito clínico-patológico com o seguimento clínico dos pacientes. Foi realizada revisão de 47 casos do Departamento de Patologia da UNIFESP e as amostras foram submetidas a exame imunohistoquímico com os marcadores proteína p53, fator de proliferação celular Ki-67 e receptor de progesterona. Verificou-se maior expressão na progressão dos diversos graus de agressividade para p53 e Ki-67 e maior frequência de receptores de progesterona nos menores graus. O grupo dos meningiomas grau I com necrose espontânea apresentou índices histológicos e imuno-histoquímicos que se aproximam dos meningiomas grau II. Isto sugere um pior prognóstico dos meningiomas grau I com necrose.

Sleep deprivation induces pathological changes in rat masticatory muscles: Role of Toll like signaling pathway and atrophy.

The aim of this study was to evaluate the Toll like signaling pathway and atrophy after sleep deprivation (SD) in rat masticatory muscles: masseter and temporal. A total of 24 animals was distributed into three groups: Control group (CTL, n = 8), subjected to SD for 96 h (SD96, n = 8) and subjected to SD for 96 h more 96 h of sleep recovery (SD96 + R, n = 8). Histopathological analysis revealed the presence of acute inflammatory cells, congested vessels, fibrosis, and high cellularity in the skeletal muscle fibers from masseter and temporal submitted to SD. These morphological alterations were not observed in the control group since neither inflammatory cells nor congested vessels were observed to this group. In the group SD96 + R, the absence of inflammation was noticed to the masseter only. In this group, COX-2 and TNF-alpha downregulation were detected when comparing to control group. MyD88 and pIKK decreased in SD96 and SD96 + R groups being pNFKBp50 downregulatated in SD96 + R. MyD88 expression increased in rats submitted to SD96 and SD96 + R in temporal when compared to control group. On the other hand, pIKK decreased the protein expression in groups SD96 and SD96 + R while pNFKBp50 showed a decreased protein expression in group SD96 only. The activation of atrophy by means of MAFbx upregulation was detected in temporal muscle in SD96 and SD96 + R when compared to control. In summary, our results show that SD is able to induce morphological alterations in rat masticatory muscles. Toll like signaling pathway and atrophy play important roles in ethiopathogenesis induced by SD, being dependent of skeletal muscle type.

Does melatonin influence the apoptosis in rat uterus of animals exposed to continuous light?

Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

Amifostine Increases FAS and Caspase-3 Expression in Colonic Tissue of Irradiated Mice.

BACKGROUND/AIM: The aim of this study was to evaluate the expression of FASL, FAS and FADD and caspase-3 in oesophagus, stomach and colonic tissues of mice irradiated in vivo by immunohistochemistry. MATERIALS AND METHODS: A total of 48 adult male C57BL mice were distributed into four groups: Ami(-)/Rad(-): Mice received 0.5 ml of 0.9% physiological saline solution (PPS) intraperitioneally (i.p.); Ami(+)/Rad(-): mice received amifostine (400mg/kg i.p.) freshly dissolved in double-distilled water; Ami(-)/Rad(+): mice received 0.5 ml of PSS i.p. 30 min before a single whole-body radiation dose of 7 Gy; Ami(+)/Rad(+): mice received 0.5 ml of an aqueous solution of 400 mg/kg amifostine i.p.30 min prior to irradiation. All groups were assigned into subgroups sacrificed at 0.5 h, 1 h, 2 h and 4 h after irradiation. RESULTS: In oesophagus and stomach tissues, we did not observe any difference between Ami(-)/ad(-), Ami(+)/Rad(-), Ami(-)/Rad(+) and Ami(+)/Rad(+) groups in the expression of FASL, FAS and FADD. The colonic tissue was the only to exhibit any difference in the expression of FAS and caspase-3 protein in the Ami(-)/Rad(+)group at 1 and 2 h. Amifostine increased FAS and caspase-3 immunoexpression when compared to the control. Immunoexpression for FASL and FADD was not remarkably different in colonic tissue. CONCLUSION: Taken together, our results demonstrate that amifostine increases FAS and caspase-3 expression in colonic tissue of irradiated mice.

The influence of sleep restriction on expression of apoptosis regulatory proteins p53, Bcl-2 and Bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

PURPOSE: The aim of this study was to evaluate whether sleep restriction (SR) could affect the mechanisms and pathways' essentials for cancer cells in tongue cancer induced by 4-nitroquinoline 1-oxide in Wistar rats. METHODS: The animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to sleep restriction for 21 days using the modified multiple platform method, which consisted of placing 5 rats in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. RESULTS: Although no histopathologic abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplastic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53, and for bcl-2. Following 12 weeks of 4NQO administration, we found significant differences between SR and control groups in p53, bax, and bcl-2 immunoexpression. CONCLUSION: Our results reveal that sleep restriction exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.

Expression of Galectins 1, 3 and 9 in normal oral epithelium, oral squamous papilloma, and oral squamous cell carcinoma.

BACKGROUND: The aim of this study was to characterize the immunohistochemical expression of galectin 1, 3, and 9 in normal oral epithelium, oral squamous papilloma, and oral squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for galectins 1, 3, and 9 was evaluated in 8 samples of normal oral squamous epithelium, 15 samples of oral squamous papilloma, and 41 samples of oral squamous cell carcinoma. Immunohistochemical data were assessed by Kruskal-Wallis non-parametric test followed by Dunn's test. For all analyzes, it was adopted the value of P <0.05 for statistical significance. RESULTS: Significant differences were found in galectin- 3 expression when comparing ordinary mucosa and oral squamous papilloma with the oral squamous cell carcinoma samples. CONCLUSION: These findings indicate that galectin-3 is closely involved in malignant transformation of oral mucosa cells.

The chemopreventive activity of apple against carcinogenesis: antioxidant activity and cell cycle control.

Apples and their derivatives are rich in phytochemicals, including flavonoids (catechins, flavonols, quercetin) and phenolic acids (quercetin glycosides, catechin, epicatechin, procyanidins), vitamins, and fibers, that confer an important antioxidant property. Chemoprevention is defined by the use of natural or synthetic agents to interfere with the progression, reverse, or inhibit carcinogenesis, thereby reducing the risk of developing clinically invasive disease. The aim of this article is to present data generated from the use of apples as a chemopreventive agent in carcinogenesis using in-vivo and in-vitro test systems. Apple and its bioactive compounds can exert chemopreventive properties as a result of antioxidant activity and cell cycle control. However, future focus of research on apple such as identifying the specific phytochemical responsible for the anticarcinogenic effect, timing of consumption, and adequate amount of apples to achieve the best preventive effect using human large randomized-controlled trials is needed. Furthermore, animal studies are also relevant for better understanding the role of this fruit in human health as well as modulation of degenerative diseases such as cancer. Therefore, this area warrants further investigation as a new way of thinking, which would apply not only to apples but also to other fruit used as promising therapeutic agents against human diseases.

Detection of galectins during malignant transformation of oral cells.

Oral cancer is a common neoplasm world-wide. The incidence and mortality have increased over the past decades. It is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. Galectins are detected in a wide variety of tissues. The expression of galectins is modulated during the differentiation of individual cells and during the development of organisms and tissues, being altered in different physiological or pathological conditions including, carcinogenesis. In this review, we will discuss the role of galectins during the malignant transformation of oral cells, in order to understand their mechanisms of the action in a several cellular activities and test systems. Certainly, such information will contribute for understanding oral cancer pathogenesis.

Chromosome breakage and cellular death are induced in oral epithelial cells of hairdressers: a preliminary study.

The aim of the present study was to comparatively evaluate genomic damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated oral mucosa cells from hairdressers using two different anatomic buccal sites: cheek mucosa and lateral border of the tongue. A total of 28 hairdressers and 30 health controls (non-exposed individuals) were included in this setting. Individuals had epithelial cells from the cheek and lateral border of the tongue mechanically exfoliated, placed in fixative and dropped in clean slides that were checked for the previously mentioned nuclear phenotypes. The results pointed out statistically significant differences (p < 0.05) of micronucleated oral mucosa cells from hairdressers in the lateral border of the tongue. Exposure to hair dyes caused an increase of other nuclear alterations closely related to cytotoxicity, such as karrhyorexis, pyknosis and karyolysis in both the oral sites evaluated. In summary, these data indicate that hairdressers are occupationally exposed to agents that are genotoxic and cytotoxic. It seems that the lateral border of the tongue is a more sensitive site to the genotoxic and cytotoxic effects of hair dyes.

Cytogenetic damage induced by mouthrinses formulations in vivo and in vitro.

The aim of the present study was to comparatively evaluate DNA damage and cellular death in cells exposed to various commercially available mouthrinses: Listerine Cepacol, Plax alcohol free, Periogard, and Plax Whitening. A total of 75 volunteers were included in the search distributed into five groups containing 15 people each for in vivo study. Exfoliated buccal mucosa cells were collected immediately before mouthrinse exposure and after 2 weeks. Furthermore, blood samples were obtained from three healthy donors for in vitro study. The micronucleus test was used to evaluate mutagenicity and cytotoxicity in vivo. The single-cell gel (comet) assay was used to determine DNA damage in vitro. After 2 weeks exposure, Periogard showed 1.8% of micronucleated cells with significant statistical differences (p < 0.05) compared to before exposure (0.27%). Plax Whitening presented high tail moment value (4.5) when compared to negative control (0.6). The addition of all mouthrinses to cells incubated with methyl methanesulfonate did not alter the number of strand breaks in the genetic material. Listerine was able to reduce genetic damage induced by hydrogen peroxide because a decrease of tail moment was noticed. The results of the present study suggest that Periogard and Plax Whitening can induce genetic damage, whereas Listerine is an antioxidant agent. Since DNA damage is considered to be prime mechanism during chemical carcinogenesis, these data may be relevant in risk assessment for protecting human health and preventing carcinogenesis.

Low-level laser irradiation, cyclooxygenase-2 (COX-2) expression and necrosis of random skin flaps in rats.

Skin flaps are still a matter of concern among surgeons, as failures can occur leading to flap necrosis. However, low-level laser irradiation has been reported as an effective tool to improve the viability of ischemic flaps, yet its mechanisms of action remain unclear. We investigated the effect of low-level laser irradiation on the viability of random skin flaps in rats and determined COX-2 expression in the flap pedicle. The study animals comprised 24 EPM-1 Wistar rats which were randomly allocated into three equal groups. A cranially based dorsal random skin flap measuring 10 × 4 cm was created in all the animals. In one group, laser irradiation was simulated (sham group), and in the other two groups the animals were irradiated at 12 points with 0.29 J at 20 mW (energy density 10.36 J/cm(2), irradiance 0.71 W/cm(2)), or with 7.3 J at 100 mW (energy density 260.7 J/cm(2), irradiance 3.57 W/cm(2)). These procedures were applied to the cranial half of the flap immediately after surgery and were repeated on days 2 and 5 after surgery. The percentage necrotic area was determined on day 7 after surgery by the paper template method. The immunohistochemical expression of COX-2 in the samples was given scores from 0 to 3. The necrotic area was smaller in group irradiated at 7.3 J compared to sham-treated group and to the group irradiated at 0.29 J (P < 0.05); there was no difference between the sham-treated group and group irradiated at 0.29 J. COX-2 expression was lower in the group irradiated at 7.3 J than in the sham-treated group and the group irradiated at 0.29 J (P < 0.001). Low-level laser therapy was effective in decreasing random skin flap necrosis in rats using a laser energy of 7.30 J per point. Laser irradiation also decreased the expression of COX-2 in the flap pedicle.

The role of metalloendopeptidases in oropharyngeal carcinomas assessed by tissue microarray.

The goal of this study was to investigate the expression of some metalloendopeptidases in squamous cell carcinomas of the oropharynx as well as its relation to histological differentiation, staging of disease, and prognosis. Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of EP24.15 and EP24.16 by means of tissue microarrays. Expression of EP24.15 or EP24.16 was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinomas of the oropharynx. In summary, our results support the notion that EP24.15 and EP24.16 are expressed in carcinoma of the oropharynx; however, these do not appear to be suitable biomarkers for histological grading, disease stage or recurrence as depicted by tissue microarrays and immunohistochemistry.

The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray.

The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue microarray by immunohistochemistry. The tumor and the adjacent normal tissues were positive for FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%, for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and 8.3%, respectively. FasL and the FADD from tumor were statistically different in relation to the histological type. Cleaved caspase 8 was statistically different in relation to clinical stage (p=0.031). The FADD from normal tissue was statistically different in relation to age (p=0.039), sex (p=0.055), clinical stage (p=0.019), and Fas was different in relation to tumor size (p=0.012). In the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and FasL and cleaved caspase 3. In the adjacent normal tissue, a correlation was observed between FasL and Fas, FasL and FADD. There was no association of another marker with sex, age, clinical stage, and survival. Our results suggest that these proteins mediate the early extrinsic apoptotic pathway in gastric cancer and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently binds to death receptor FADD signaling activation of the extrinsic apoptotic pathway. In this phase, there was inhibition of caspase 8 and, consequently, decreased apoptosis.

Ras gene mutation is not related to tumour invasion during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

BACKGROUND: The aim of this study was to investigate whether mutations in the genes H-ras and K-ras were related to the mechanism of invasion as a result of the immunoexpression of H-Ras, Ki-67, alpha-smooth muscle actin (SMA) and vascular endothelial growth factor (VEGF) during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. METHODS: Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 and 20 weeks. Ten animals were used as negative control. RESULTS: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, Ki-67 was overexpresssed in the 'normal' oral epithelium. In pre-neoplastic lesions at 12 weeks following carcinogen exposure, the levels of Ki-67 were increased (P < 0.05) when compared to negative control. Ki-67, alpha-SMA and VEGF were also overexpressed in squamous cell carcinomas induced after 20 weeks of treatment with 4NQO. No significant statistical differences (P > 0.05) were found in H-ras protein expression for all experimental periods evaluated that corresponded to normal oral mucosa, hyperplasia, dysplasia and squamous cell carcinomas. In the same way, no mutations in H-ras or K-ras genes were found. CONCLUSIONS: Our results support the idea that expression of Ki-67 plays a crucial role during malignant transformation being closely related to neoplastic conversion of the oral mucosa cells. However, it seems that mutations in the ras genes are not involved to experimental tongue carcinogenesis induced by 4NQO.

Phosphorylation and cytoplasmic localization of MAPK p38 during apoptosis signaling in bone marrow granulocytes of mice irradiated in vivo and the role of amifostine in reducing these effects.

We studied p38 phosphorylation and its intracellular localization during p53 and Puma (a p53 upregulated modulator of apoptosis) apoptotic signaling pathway in bone marrow granulocytes in mice irradiated in vivo and the role of the radioprotector amifostine in ameliorating these responses. Sixty-four C57BL mice were randomly assigned in two non-irradiated (Ami-/rad- and Ami+/rad-) and two irradiated (Ami-/rad+ and Ami+/rad+) groups. Animals received 400mg/kg of amifostine i.p. 30 min prior to a single whole body radiation dose of 7Gy. The experiments were performed using immunohistochemistry for caspase-3, cleaved caspase-3, p53, p-p53 (Ser 15), Puma, p38 and p-p38 (Thr 180/Tyr 182) protein expression. In addition transmission electron microscopy was used for ultrastructural characterization of apoptosis. Data showed that: (i) amifostine significantly reduced the number of apoptotic cells, (ii) p-p53 and Puma proteins were strongly immunostained in granulocytes after irradiation (Ami-/rad+), (iii) amifostine decreased the immunostaining of the proteins (Ami+/rad+), (iv) p38 was immunolocalized in physiological conditions in the nucleus and cytoplasm of granulocytes and neither radiation nor amifostine changed the protein immunostaining or its subcellular distribution, but influenced its activation, (v) radiation-induced p38 phosphorylation and its cytoplasmic accumulation during apoptosis signaling in granulocytes after whole body high radiation dose and amifostine markedly reduced these effects.

Effects of melatonin on histomorphology and on the expression of steroid receptors, VEGF, and PCNA in ovaries of pinealectomized female rats.

OBJECTIVE: To evaluate the effect of melatonin both on the ovaries of pinealectomized female rats through histomorphometric analysis and on steroid receptors, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) expression. DESIGN: Experimental study. SETTING: Federal University of São Paulo, Brazil. ANIMAL(S): Forty female rats. INTERVENTION(S): Forty rats were divided equally into four groups: GI-vehicle without surgery; GII--surgery without removal of the pineal gland (sham); GIII--pinealectomized with vehicle; and GIV--pinealectomized with melatonin treatment. After treatment for 3 consecutive months, the animals were killed and their ovaries removed for analysis. MAIN OUTCOME MEASURE(S): Estrogen and progesterone receptors, histologic and immunohistochemical analysis. RESULT(S): The GIII samples presented signals of proliferation on ovarian surface epithelium and interstitial cells as well as high expressions of PCNA and VEGF in those structures compared with GI, GII, and GIV. Also, the levels of progesterone receptor (fmol/g) in ovaries of GIII (250.6 ± 32.4) were significantly lower than in those of GI (429.0 ± 23,8), GII (442.3 ± 30.2), and GIV (564.1 ± 78.7). The levels of progesterone in GIII were superior to those in GI, GII, and GIV. CONCLUSION(S): Our findings suggest that melatonin may attenuate proliferation in ovarian structures and increase the number of luteal bodies as well as the levels of progesterone receptor.

Expression of p27, p21(WAF/Cip1), and p16(INK4a) in normal oral epithelium, oral squamous papilloma, and oral squamous cell carcinoma.

AIM: To characterize the immunohistochemical expression of p27, p21(WAF/Cip1) and p16(INK4a) in normal oral epithelium, oral squamous papilloma and oral squamous cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining for p27, p21(WAF/Cip1) and p16(INK4a) was evaluated in 32 samples of normal oral squamous epithelium, 30 samples of oral squamous papilloma, and 34 samples of oral squamous cell carcinoma. RESULTS: Statistically significant differences (p<0.05) were found in p27 expression when comparing ordinary mucosa and oral squamous papilloma with the oral squamous cell carcinoma samples. Regarding p21(WAF/Cip1) expression, no statistically significant differences (p>0.05) were noticed. In the same way, no significant statistically differences (p>0.05) were observed for p16(INK4a) among groups. CONCLUSION: Taken together, these findings indicate that p27 is closely involved in malignant transformation of oral mucosa cells, and may be a reliable biomarker for this purpose.

Expression profiling of cell cycle regulatory proteins in oropharyngeal carcinomas using tissue microarrays.

AIM: The aim of this study was to investigate the expressions of cell cycle regulatory proteins such as p53, p16, p21, and Rb in squamous cell carcinoma of the oropharynx and their relation to histological differentiation, staging of disease, and prognosis. PATIENTS AND METHODS: Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of p53, p16, p21, and Rb by means of tissue microarrays. RESULTS: Expression of p53, p21, p16 and Rb was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinoma of the oropharynx. CONCLUSION: Taken together, our results suggest that p53, p16, p21 and Rb are not reliable biomarkers for prognosis of the tumor severity or recurrence in squamous cell carcinoma of the oropharynx as depicted by tissue microarrays and immunohistochemistry.