Mucinous neoplasm of the appendix:A case report and review of literature

BACKGROUND Appendiceal mucinous neoplasms(AMNs),although not classified as rare,are relatively uncommon tumors most often discovered incidentally during colorectal surgery.Accurate identification of AMNs is difficult due to non-specific sym-ptoms,overlapping tumor markers with other conditions,and the potential for misdiagnosis.This underscores the urgent need for precision in diagnosis to pre-vent severe complications.CASE SUMMARY This case report describes the unexpected discovery and treatment of a low-grade AMN(LAMN)in a 74-year-old man undergoing laparoscopic hemicolectomy for transverse colon adenocarcinoma(AC).Preoperatively,non-specific gastroin-testinal symptoms and elevated tumor markers masked the presence of AMN.The tumor,presumed to be an AMN peritoneal cyst intraoperatively,was con-firmed as LAMN through histopathological examination.The neoplasm exhibited mucin accumulation and a distinct immunohistochemical profile:Positive for Ho-meobox protein CDX-2,Cytokeratin 20,special AT-rich sequence-binding protein 2,and Mucin 2 but negative for cytokeratin 7 and Paired box gene 8.This profile aids in distinguishing appendiceal and ovarian mucinous tumors.Postoperative recovery was uncomplicated,and the patient initiated adjuvant chemotherapy for the colon AC.CONCLUSION This case highlights the diagnostic complexity of AMNs,emphasizing the need for vigilant identification to avert potential complications,such as pseudomyxoma peritonei.

IgSF11-mediated phosphorylation of pyruvate kinase M2 regulates osteoclast differentiation and prevents pathological bone loss

Osteoclasts are primary bone-resorbing cells,and receptor-activated NF-k B ligand(RANKL)stimulation is the key driver of osteoclast differentiation.During late-stage differentiation,osteoclasts become multinucleated and enlarged(so-called“maturation”),suggesting their need to adapt to changing metabolic demands and a substantial increase in size.Here,we demonstrate that immunoglobulin superfamily 11(Ig SF11),which is required for osteoclast differentiation through an association with the postsynaptic scaffolding protein PSD-95,regulates osteoclast differentiation by controlling the activity of pyruvate kinase M isoform2(PKM2).By using a system that directly induces the activation of Ig SF11 in a controlled manner,we identified PKM2 as a major Ig SF11-induced tyrosine-phosphorylated protein.Ig SF11 activates multiple Src family tyrosine kinases(SFKs),including c-Src,Fyn,and Hc K,which phosphorylate PKM2 and thereby inhibit PKM2 activity.Consistently,Ig SF11-deficient cells show higher PKM2activity and defective osteoclast differentiation.Furthermore,inhibiting PKM2 activities with the specific inhibitor Shikonin rescues the impaired osteoclast differentiation in Ig SF11-deficient cells,and activating PKM2 with the specific activator TEPP46 suppresses osteoclast differentiation in wild-type cells.Moreover,PKM2 activation further suppresses osteoclastic bone loss without affecting bone formation in vivo.Taken together,these results show that Ig SF11 controls osteoclast differentiation through PKM2 activity,which is a metabolic switch necessary for optimal osteoclast maturation.

Liver pathology of hepatitis C,beyond grading and stagingof the disease

Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other nonviral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection.

Acute myeloid leukemia in the era of precision medicine:recent advances in diagnostic classification and risk stratification

Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of pancreatic cysts by combined cytopathology and cystic content analysis

Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, endoscopic ultrasound(EUS)-guided fine-needle aspiration(FNA) has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion, diagnose malignancy and collect cyst fluid for further diagnostic studies, such as pancreatic enzyme levels, molecular analysis and other tumor biomarkers. The current review will focus on EUSguided FNA and the cytological diagnosis for pancreatic cysts.

The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.

Do tensile and shear forces exerted on cells influence mechanotransduction through stored energy considerations?

All tissues in the body are subjected externally to gravity and internally by collagenfibril and cellular retractive forces that create stress and energy equilibrium required for homeostasis.Mechanotransduction involves mechanical work(force through a distance)and energy storage as kinetic and potential energy.This leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue components.It involves the application of energy directly to cells through integrin-mediated processes,cell-cell connections,stretching of the cell cytoplasm,and activation of the cell nucleus via yes-associated protein(YAP)and transcriptional coactivator with PDZ-motif(TAZ).These processes involve numerous complexes,intermediate molecules,and multiple pathways.Several pathways have been identified from research studies on vertebrate cell culture and from studies in invertebrates.These pathways involve mechanosensors and other molecules that activate the pathways.This review discusses the mitogen-activated protein kinase(MAPK)family,Hippo,Hedgehog,and Wingless-related integration site(WNT)/βcatenin signaling pathways.The mediators covered includeβcatenin,ion channels,growth factors,hormone receptors,members of the Ras superfamily,and components of the linker of nucleoskeleton and cytoskeleton(LINC)complex.However,the interrelationship among the different pathways remains to be clarified.Integrin-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagenfibril stretching.This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin pathway.These alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and TAZ.These coactivators then penetrate through the nuclear pores and influence nuclear cell function.Alteration in the balance of forces and energy applied to cells and tissues is hypothesized to shift the cell-extracellular matrix mechanical equilibrium by modifying mechanotransduction.The shift in equilibrium can lead to either tissue synthesis,genetic modifications,or promotefibrotic diseases,including epithelial cell-derived cancers,depending on the local metabolic conditions.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural regeneration.Both intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following injury.At the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to regenerate.Recent works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of regeneration.The role of glia in neuron regeneration has long been studied.

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

Blastomas of the digestive system in adults:A review

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

Stercoral perforation of the cecum:A case report

BACKGROUND With less than 90 reported cases to date,stercoral perforation of the colon is a rare occurrence.Stercoral ulceration is thought to occur due to ischemic pressure necrosis of the bowel wall,which is caused by the presence of a stercoraceous mass.To underscore this urgent surgical situation concerning clinical presentation,surgical treatment,and results,we present the case of a 66-year-old man with a stercoral perforation.CASE SUMMARY A 66-year-old man with a history of hypertension,hyperlipidemia,and gout presented at the emergency department with lower abdominal pain and a low-grade fever lasting for a few hours.Abdominal computed tomography indicated a suspected bezoar(approximately 7.6 cm)in the dilated cecum,accompanied by pericolic fat stranding,mild proximal dilatation of the ileum,pneumoperitoneum,and minimal ascites.Intraoperatively,feculent peritonitis with isolated cecal perforation were observed.Consequently,a right hemicolectomy with peritoneal lavage was performed.A histopathological examination supported the intraoperative findings.CONCLUSION In stercoral perforations,a diagnosis should be diligently pursued,especially in older adults,and prompt surgical intervention should be implemented.

Cellular angiofibroma arising from the rectocutaneous fistula in an adult: A case report

BACKGROUND Rectocutaneous fistulae are common.The infection originates within the anal glands and subsequently extends into adjacent regions,ultimately resulting in fistula development.Cellular angiofibroma(CAF),also known as an angiomy ofibroblastoma-like tumor,is a rare benign soft tissue neoplasm predominantly observed in the scrotum,perineum,and inguinal area in males and in the vulva in females.We describe the first documented case CAF that developed within a rectocutaneous fistula and manifested as a perineal mass.CASE SUMMARY In the outpatient setting,a 52-year-old male patient presented with a 2-year history of a growing perineal mass,accompanied by throbbing pain and minor scrotal abrasion.Physical examination revealed a soft,well-defined,non-tender mass at the left buttock that extended towards the perineum,without a visible opening.The initial assessment identified a soft tissue tumor,and the laboratory data were within normal ranges.Abdominal and pelvic computed tomography(CT)revealed swelling of the abscess cavity that was linked to a rectal cutaneous fistula,with a track-like lesion measuring 6 cm×0.7 cm in the left perineal region and attached to the left rectum.Rectoscope examination found no significant inner orifices.A left medial gluteal incision revealed a thick-walled mass,which was excised along with the extending tract,and curettage was performed.Histopathological examination confirmed CAF diagnosis.The patient achieved total resolution during follow-up assessments and did not require additional hospitalization.CONCLUSION CT imaging supports perineal lesion diagnosis and management.Perineal angiofibromas,even with a cutaneous fistula,can be excised transperineally.

Therapeutic Effects of Myriocin in Experimental Alcohol-Related Neurobehavioral Dysfunction and Frontal Lobe White Matter Biochemical Pathology

Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.

Clear Cell Pleomorphic Dermal Sarcoma: A Case Report and Literature Review

Introduction: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are one spectrum of rare cutaneous neoplasms that typically arise in sun-exposed skin of older population. AFX/PDS is essentially diagnosis of exclusion requiring Immunohistochemical work-up to exclude other types of tumors. Case Report: We present a case involving an ulcerated solitary lesion on the scalp of an elderly man. Histological examination revealed that the dermal tumor was composed of large pleomorphic, epithelioid, and spindle cells with clear cytoplasm. These cells were negative for cytokeratins, melanocytes and smooth muscle markers, but positive for CD10. These findings are consistent with a diagnosis of clear cell (CC) PDS. Conclusion: PDS is a low-grade malignancy that can recur locally and metastasize, which is distinguished from AFX by its larger size and the presence of aggressive histopathologic features including deeper invasion into the subcutaneous tissue, tumor necrosis, and lymphovascular and/or perineural involvement. Among several histopathologic variants, the CC variant is extremely rare with only two cases of PDS reported in the literature to date.

Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

因为早察觉和治疗为病人的医药管理是批评的，为早前列腺癌症诊断的新奇简历标记的鉴定是高度重要的。在基础房间层和地下室膜的连续性的混乱为高级职业人员静电干扰 intraepithelial 瘤形成(HGPIN ) 的前进是必要的到在人的前列腺的侵略腺癌。涉及变换到侵略显型的分子是强烈审查的题目。我们以前报导了矩阵 metalloproteinase-26 (MMP-26 ) 经由地下室膜蛋白质并且由激活 MMP-9 的酶原形式的劈开支持人的前列腺癌症房间的侵略。而且，我们发现了 metalloproteinases-4 (TIMP-4 ) 的那个织物禁止者是大多数有势力 MMP-26 的内长的禁止者。这里，我们更高示威(p【0.0001 ) 在 HGPIN 和癌症的 MMP-26 和 TIMP-4 表示，与非肿瘤的 acini 相比。他们的表示层次在 HGPIN 是最高的，但是在一样的纸巾在侵略癌症(为各个的 p【0.001 ) 衰退。连续前列腺癌症织物节染色的 Immunohistochemical 建议 MMP-26 和 TIMP-4 的 colocalization。现在的学习显示 MMP-26 和 TIMP-4 可以在 HGPIN 的变换期间起一个不可分的作用到侵略癌症并且可以也为早前列腺癌症诊断用作标记。房间研究(2006 ) 16：750-758。做 i：10.1038/sj .cr.7310089；出版联机 2006 年 8 月 29 日。

Hepatic inflammatory pseudotumor presenting in an 8-year-old boy: A case report and review of literature

Hepatic inflammatory pseudotumors are uncommon benign lesions.Accurately diagnosing hepatic inflammatory pseudotumor can be very challenging because the clinical presentation and radiological appearances are nonspecific and cannot be certainly distinguished from malignant neoplastic processes.Herein,we present a case of hepatic IPT in an 8-yearold boy who presented to clinic with a 3-mo history of a tender hepatic mass,fever of unknown origin,and9-kg weight loss.The physical examination was notable for tender hepatomegaly.Laboratory investigations were notable for a normal hepatic profile and elevated erythrocyte sedimentation rate and C-reactive protein.A T2-attenuated magnetic resonance imaging scan of the abdomen showed a 4.7 cm x 4.7 cm x 6.6cm,contrast-enhancing,hyper-intense,well-defined lesion involving the right hepatic lobe.In view of the unremitting symptoms,tender hepatomegaly,thrombosed right hepatic vein,nonspecific radiological findings,and high suspicion of a deep-seated underlying infection or malignancy,a right hepatic lobectomy was recommended.Microscopically,the hepatic lesion exhibited a mixture of inflammatory cells(histiocytes,plasma cells,mature lymphocytes,and occasional multinucleated giant cells) in a background of dense fibrous tissue.Immunohistochemically,the cells stained negative for SMA,ALK-1,CD-21 and CD-23,diffusely positive for CD-68,and focally positive for lgG4.The final histopathological diagnosis was consistent with hepatic IPT.At the postoperative 4-mo follow-up,the patient was asymptomatic without radiological evidence of recurrence.

Combined goblet cell carcinoid and mucinous cystadenoma of the vermiform appendix

Goblet cell carcinoid is an uncommon primary tumor of the vermiform appendix, characterized by dual endocrine and glandular differentiation. Whether goblet cell carcinoid represents a morphological variant of appendiceal classical carcinoid or a mucin-producing adenocarcinoma is a matter of conjecture. Rare cases of goblet cell carcinoid with other concomitant appendiceal epithelial neoplasms have been documented. In this report, we describe a rare case of combined appendiceal goblet cell carcinoid and mucinous cystadenoma, and discuss the possible histopathogenesis of this combination.

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P<0.01),sporadic dysplasia(68.80±4.42,P<0.01),sporadic cancer(74.80±4.91,P<0.001),and CAC(57.50±5.11,P<0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P<0.05,P<0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P<0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P<0.001 vs normal,P<0.001 vs CAC)and sporadic CRC(0.47±0.23,P<0.001 vs normal,P<0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer.