The Clinicopathological Characteristics of Young-Onset Versus Adult-Onset Colorectal Cancer: A Tertiary Hospital-Based Study.

Background: The prevalence of colorectal cancer (CRC) among young individuals is rising worldwide, especially in Malaysia. Investigations are currently employed to distinguish the features of young-onset CRC (YOCRC) from adult-onset CRC (AOCRC). This study aimed to compare the characteristics of patients with YOCRC and AOCRC diagnosed at Hospital Universiti Sains Malaysia (HUSM). Methods: This was a retrospective study of CRC cases from January 2013 to December 2021. The details of YOCRC (< 50 years old) and AOCRC (≥ 50 years old) patients were retrieved from the laboratory system and medical records. The Pearson's chi-square test, Fisher's exact test and multiple logistic regression were used to compare the AOCRC and YOCRC cases. Statistical significance was defined at a P-value of ≤ 0.05. Results: The AOCRC (254/319, 79.6%) was more prevalent than YOCRC (65/319, 20.4%), with a predominance of males (53.9%) and Malay sub-population (90.2%). AOCRC and YOCRC shared similarities in left-sided location, high occurrence of adenocarcinoma with moderately differentiated histology and advanced stage of diagnosis. More patients with YOCRC (23.1%) had a family history of cancer than patients with AOCRC. YOCRC also differed from AOCRC by having more specific histological subtypes, such as mucinous adenocarcinoma (15.4%) and signet ring carcinoma (6.2%). In addition, patients with YOCRC commonly presented with a low density of tumour-infiltrating lymphocytes (TILs) (60%). Multiple logistic regression showed a family history of CRC (adjusted odds ratio [AOR] = 3.75, P = 0.003) and histological type (AOR = 15.21, P < 0.001) are more likely to cause YOCRC than diabetes (AOR = 0.06, P < 0.001) and hypertension (AOR = 0.14, P < 0.001) comorbidities, which are associated with AOCRC. Conclusion: Our descriptive study presented the epidemiological and histopathological characteristics of AOCRC and YOCRC in HUSM, providing current information on distinguishing features between the groups.

An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer.

The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72−0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer.

Evaluation of HPV 16 and HPV 18 Oncoprotein Expression as Alternative Diagnostic Tools in Cervical Lesion.

OBJECTIVE: The study aimed to evaluate E6 and E7 oncoproteins of HPV16 and HPV18 expression in formalin - fixed paraffin embedded (FFPE) tissue in different grades of the cervical lesion and evaluate the potential use of E6 and E7 oncoproteins derived from HPV 16 and 18 as diagnostic protein biomarkers for triaging cervical lesions. METHODOLOGY: A total of 102 FFPE cervical tissues were collected from 2 tertiary hospitals and immunohistochemical reactivity staining of E6 and E7 oncoproteins of HPV16 and HPV18 were evaluated using immunoreactive scoring (IRS) system and analysed statistically. RESULT: The result showed an increased oncoprotein expression with the progression of cervical lesions. There is a statistically significant association between histology grade and HPV16/18-E6 expression (p = 0.028). However, there are no significant association of histological grade to HPV16-E7 immunoreactivity score (p = 0.264) and HPV18-E7 (p=0.080). CONCLUSION: The immunohistochemical expression of HPV oncoproteins is a potential alternative diagnostic tool applicable in a low-resource laboratory setting. The advantage of the histochemical evaluation is that this method is simpler to apply and less expensive in comparison to in situ mRNA hybridization. Nevertheless, our study also found that antibodies against HPV that are commercially available suffer quite substantial specificity issues such as background staining and inconsistency between different batches. Hence, the utilization of antibody-based staining warrants stringent quality control.

Dataset of acute oral toxicity and subacute neurotoxicity risk assessments of flavonoid-enriched fraction extracted from Oroxylum Indicum on Sprague Dawley rats.

Oroxylum indicum is a medicinal herb that garnered enormous attention in drug discovery for human diseases such as neurodegenerative, cardiovascular, arthritis and hepatitis diseases. Pharmacokinetic study confirmed that the pharmacological actions of this herb are associated with its prominent flavonoid bioactive components. Here, the data set of liquid chromatography-mass spectroscopy (LC-MS), neurological functions, relative organ weight (ROW), hematological, biochemical and histopathological parameters of flavonoid-enriched fraction (FEF)-treated Sprague Dawley (SD) rats were presented. The data set was generated from three study groups namely: Sighting Study, Acute Toxicity Study and Subacute Neurotoxicity Study with study duration of 14 days (for Sighting Study and Acute Toxicity Study) and 28 days (for Subacute Neurotoxicity Study) by strictly following the procedures set in Organisation for Economic Co-operation and Development (OECD) Guidelines 420 and 424 in vivo. Rats in sighting study were treated with dosage of 5, 50, 300 and 2000 mg/kg FEF (n = 1/dosage/gender), respectively, and were observed for mortality, toxicity signs and behavioural changes. The highest dosage at which none of the animal showed sign of mortality in the sighting study was selected as the test dosage for subsequent acute toxicity study (n = 5/dosage/gender). Meanwhile, for subacute neurotoxicity study, SD rats (n = 5/dosage/gender) were treated with repeated dosage of 50 mg/kg for 28 days. Neurological behaviours of treated rats were observed daily, while their body weight were measured weekly. Whole blood was collected at the end of the study via cardiac puncture into ethylenediaminetetraacetic acid (EDTA) tubes for hematological evaluation that included the measurements of red blood cells (RBC), hemoglobin (Hb), packed cell volumes (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet, white blood cells (WBC) count and WBC differentials. Meanwhile, blood serum were collected into slow sand filter (SST) tubes for biochemical evaluation that included measurements of total protein (TP), albumin, bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Vital organs such as brain, liver, kidneys, heart, lungs and reproductive organs also were collected, sliced and stained with hematoxylin and eosin (H&E) at the end of the study for histopathological assessments.

Atypical Presentation of Necrotizing Sialometaplasia of the Hard Palate: A Diagnostic Dilemma.

Necrotizing sialometaplasia refers to a benign, uncommon, and self-limiting inflammatory reaction concerning the salivary gland tissue, which both clinically and histologically may be easily mistaken for mucoepidermoid carcinoma or squamous cell carcinoma. This may cause irrelevant surgical intervention. Minor salivary glands are the most commonly affected salivary gland, with the hard palate being the most usual site. However, it can involve the other areas in which salivary gland tissue is present in the other oral subsites and pharyngeal areas. Due to the lack of knowledge about this entity and its histological similarities with carcinomas, particularly mucoepidermoid carcinoma, the differential diagnosis of this lesion is difficult. Local ischemia is thought to be the primary cause, leading to the pathogenesis of necrotizing sialometaplasia, and the infiltration of local anesthesia following dental procedures at the palatal region is the leading cause.

Anaplastic Pleomorphic Xanthoastrocytoma: A Rare Variant of Astrocytoma.

Pleomorphic xanthoastrocytoma (PXA) is a rare glioma that affects 1% of astrocytic tumors. It most commonly affects children and teenagers. PXA cases with an anaplastic histopathological subtype have been reported in recent years. It was recently classified as a separate subtype in the 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors. A 48-year-old healthy gentleman presented with progressive right upper limb weakness. CT and MRI of the brain were done, which showed an intra-axial supratentorial tumor. A diagnosis of high-grade glioma was initially made based on its imaging features. The histopathological study came back as anaplastic pleomorphic xanthoastrocytoma. After a discussion with the neurosurgical and oncology teams, a decision was made to treat the patient with radiotherapy. In this case report, we describe a rare case of PXA with anaplastic characteristics.

The potential neuroprotective effects of stingless bee honey.

Tropical Meliponini bees produce stingless bee honey (SBH). Studies have shown beneficial properties, including antibacterial, bacteriostatic, anti-inflammatory, neurotherapeutic, neuroprotective, wound, and sunburn healing capabilities. High phenolic acid and flavonoid concentrations offer SBH its benefits. SBH can include flavonoids, phenolic acids, ascorbic acid, tocopherol, organic acids, amino acids, and protein, depending on its botanical and geographic origins. Ursolic acid, p-coumaric acid, and gallic acid may diminish apoptotic signals in neuronal cells, such as nuclear morphological alterations and DNA fragmentation. Antioxidant activity minimizes reactive oxygen species (ROS) formation and lowers oxidative stress, inhibiting inflammation by decreasing enzymes generated during inflammation. Flavonoids in honey reduce neuroinflammation by decreasing proinflammatory cytokine and free radical production. Phytochemical components in honey, such as luteolin and phenylalanine, may aid neurological problems. A dietary amino acid, phenylalanine, may improve memory by functioning on brain-derived neurotrophic factor (BDNF) pathways. Neurotrophin BDNF binds to its major receptor, TrkB, and stimulates downstream signaling cascades, which are crucial for neurogenesis and synaptic plasticity. Through BDNF, SBH can stimulate synaptic plasticity and synaptogenesis, promoting learning and memory. Moreover, BDNF contributes to the adult brain's lasting structural and functional changes during limbic epileptogenesis by acting through the cognate receptor tyrosine receptor kinase B (TrkB). Given the higher antioxidants activity of SBH than the Apis sp. honey, it may be more therapeutically helpful. There is minimal research on SBH's neuroprotective effects, and the related pathways contribute to it is unclear. More research is needed to elucidate the underlying molecular process of SBH on BDNF/TrkB pathways in producing neuroprotective effects.

Submandibular Gland Basal Cell Adenoma.

Introduction: Basal cell adenoma (BCA) is a rare benign epithelial tumour of the salivary gland majorly involving the parotid gland, and rarely the submandibular gland. Case Report: We describe a rare case of BCA of the submandibular gland diagnosed preoperatively using fine needle aspiration cytology in a 60-year-old woman presenting with painless submandibular swelling. The surgery went uneventfully, and the histopathological examination confirmed the diagnosis. Conclusions: BCA can be accurately diagnosed only through histological observations due to its resemblance to various benign and malignant salivary and non-salivary gland tumours, which are difficult to biopsy.

Epidermal Growth Factor Receptor Gene Mutation Detection in Histology and Cytology Specimens of Primary Lung Adenocarcinoma: Immunohistochemistry Versus the Molecular Method.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene in lung adenocarcinoma is associated with good clinical response to EGFR-tyrosine kinase therapy. The two most common EGFR gene mutations, representing 80 to 90%, are the E746-A750 deletion in exon 19 and the L858R point mutation in exon 21. MATERIALS AND METHODS: We have conducted the study to evaluate immunohistochemistry's performance in detecting the E746-A750 deletion in exon 19 of the EGFR gene in primary lung adenocarcinoma cases. This study examined 133 cases of primary lung adenocarcinoma for three years duration. The selected cases were tested for EGFR gene mutations by real-time PCR by a reference laboratory. Most cases (124) were diagnosed by tissue biopsy, though nine used cell block cytology. We performed an immunohistochemistry test on 75 cases that contained adequate diagnostic material in the paraffin block. RESULTS: The test result was scored as 0 to 3+, based on the staining intensity and percentage of positive tumor cells. We evaluated the immunohistochemistry test's sensitivity and specificity compared to the EGFR gene mutations by real-time PCR. There was a significant association between gender, smoking status, and the EGFR gene mutations (P < 0.001). The overall sensitivity and specificity of the immunohistochemistry test were 40% and 100%, respectively. The positive predictive value and negative predictive values were 100% and 76.9%, each. CONCLUSIONS: The immunohistochemistry has high specificity but low sensitivity in the detection of E746-A750 deletion in exon 19 of the EGFR gene. The mutation-specific antibody used in this study was unable to detect other uncommon variants of exon 19 deletions. With high specificity value, immunohistochemistry may provide an adjunct to molecular testing for detecting the most common EGFR gene mutations in cases of a low cellularity sample, financially-limited situations, or in critically ill cases where urgent targeted therapy is needed.

Evaluation of PathTezt™, a Liquid-Based Cytology System.

Liquid-based preparation (LBP) cytology is commonly used in most laboratories these days due to its convenience and reliable results for the cervical cancer screening program. The PathTezt™ Liquid-based Pap smear is a second-generation LBP, which uses a filter-based concentration technique in processing the sample. OBJECTIVE: This study was done to evaluate the cellular fixation, morphology, quality of smear in gynae cytology, and diagnostic interpretation of cervical cytological smears produced by the PathTezt liquid-based processor. MATERIALS AND METHODS: A total of 400 pap smear samples were taken and processed using the PathTezt 2000 processor. The slides were evaluated in terms of sample adequacy, percentage of the circle covered by epithelial cells, cellular distribution, obscuring factors, and cell fixation. RESULTS: About 95.25% (381) of the samples were satisfactory for the evaluation. In 19 (4.75%) of the samples, epithelial cells covered less than 50% of the circle. A sample with good cellular distribution was seen in 92% of the cases, while 354 (88.5%) samples showed minimal inflammatory background. Almost all the smears (95.75%) had no erythrocytes in the background. All smears showed good quality fixation features toward nuclear, cytoplasm, and microorganisms. The total performance rate was 99%. CONCLUSION: Although the PathTezt liquid-based processor is still new compared to other first-generation LBP, the smears produced by this method were of high quality and it was cost-effective.

Evaluation Study of Intraoperative Cytology Smear and Frozen Section of Glioma.

OBJECTIVE: Glioma is the commonest primary malignant brain tumour. Diagnosis is made based on cytology smear, frozen section and histopathological examination. Intraoperative pathological diagnosis using either cytology smear, frozen section or combination of both, plays a crucial role in patient's future management and prognosis. This study aims to determine the accuracy of cytology smear and frozen section in glioma, and to compare the difference between both techniques. METHODS: A cross-sectional study was conducted involving 22 cases of glioma diagnosed intraoperatively from January 2013 until August 2019 in Hospital Universiti Sains Malaysia. The selected tissues were processed for cytology smear and frozen section. The remaining tissues were proceeded for paraffin section. The diagnosis was categorized as either low-grade or high-grade glioma based on cellularity, nuclear pleomorphism, mitotic count, microvascular proliferation and necrosis. The sensitivity and specificity of frozen section and cytology smears were determined based on paraffin section being as the gold standard. The accuracy of both techniques was compared using statistical analysis. RESULTS: The overall sensitivity and specificity of cytology smear were 100% and 76.9%, respectively. Meanwhile, the sensitivity and specificity of frozen section were 100% and 84.6%. There was no significant difference in diagnostic accuracy between cytology smear and frozen section in glioma (p>0.05). CONCLUSION: Cytology smears provides an alternative method for frozen section due to good cellularity and morphology on smear. Cytology smear is rapid, inexpensive, small amount of tissue requirement and less technical demand. This finding may benefit to the hospital or treatment centres where frozen section facility is unavailable.

Diagnostic Accuracy of Cytology Smear and Frozen Section in Glioma

Glioma is the commonest primary intracranial tumour and it has been the most predominant tumour in many studies. It accounts for 24.7% of all primary brain tumour and 74.6% of malignant brain tumour. Intraoperative diagnosis plays a crucial role in determining the patient management. Frozen section has been the established technique in providing rapid and accurate intraoperative diagnosis. However due to some disadvantages like ice crystal artefact, high expenditure and requirement of skilled technician, there is increase usage of cytology smear either replacing or supplementing frozen section technique. The aim of this review is to determine the diagnostic accuracy of cytology smear and frozen section in glioma and to see whether there is significant difference between those techniques. The overall diagnostic accuracy for frozen section in glioma ranging from 78.4% to 95% while for cytology smear, the diagnostic accuracy ranging from 50% to 100%. Based on certain literatures, no statistically difference was observed in diagnostic accuracy of cytology smear and frozen section. Thus, cytology smear provides an alternative method in establishing intraoperative diagnosis. Both cytology smear and frozen section are complimentary to each other. It is recommended to use both techniques to improve the diagnostic accuracy in addition with adequate knowledge, clinical history, neuroimaging and intraoperative findings.

Histological changes of female reproductive organs subjected to different jumping exercise intensities and honey supplementation in rats.

BACKGROUND: We assessed histopathological changes of ovaries and uterus in female rats subjected to different jumping exercise intensities combined with honey supplementation at one g/kg body weight/day. METHODS: A total of 72 rats were divided into six groups, 12 rats in each: control (C), 20 and 80 jumps (20E, 80E), honey (H), and 20 and 80 jump with honey (20EH, 80EH). RESULTS: The endometrium was significantly thicker in the rats in H, 20EH and 80EH groups compared to C, 20E, and 80E. The myometrium thickness was significantly lower in 80E and significantly higher in 80EH compared to C, respectively. There was significantly higher myometrium thickness in 20EH and 80EH compared to 20E and 80E and H. The number of glands of the uterus in 20E and 80E was significantly lower than C. However, there was a significantly higher number of glands in H, 20EH, and 80EH compared to 20E and 80E. The numbers of uterus vessels were significantly lower in 80E compared to 20E. However, the numbers of vessels were significantly higher in H, 20EH, and 80EH compared to 80E. The number of ovarian haemorregia was significantly lower in 20E, 80E, H, 20EH, and 80EH compared to C. The number of corpora lutea was significantly lower in 80EH, H, 80E, and 20E compared to C. However, the number of corpora lutea was significantly higher in 20EH compared to J20 and H. CONCLUSION: This study suggested that jumping exercises in particularly high-intensity exercise may induce histopathological changes in uterus and ovary in rats, and honey supplementation may ameliorate these effects.

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice.

Tumor-associated macrophages (TAMs) as immune cells within the tumor microenvironment have gained much interests as basic science regarding their roles in tumor progression unfolds. Better understanding of their polarization into pro-tumoral phenotype to promote tumor growth, tumor angiogenesis, immune evasion, and tumor metastasis has prompted various studies to investigate their clinical significance as a biomarker of predictive and prognostic value across different cancer types. Yet, the methodologies to investigate the polarization phenomena in solid tumor tissue vary. Nonetheless, quantifying the ratio of M1 to M2 TAMs has emerged to be a prevailing parameter to evaluate this polarization phenomena for clinical application. This mini-review focuses on recent studies exploring clinical significance of M1/M2 TAM ratio in human cancer tissue and critically evaluates the technicalities and challenges in quantifying this parameter for routine clinical practice. Immunohistochemistry appears to be the preferred methodology for M1/M2 TAM evaluation as it is readily available in clinical laboratories, albeit with certain limitations. Recommendations are made to standardize the quantification of TAMs for better transition into clinical practice and for better comparison among studies in various populations of patients and cancer types.

Potential Role of E4 Protein in Human Papillomavirus Screening: a Review

In 2006, cervical cancer was reported as the second most common cancer in women of Malaysia. This type of cancer has been shown to correlate with persistent high risk human papillomavirus (HPV) infection. Although HPV is well known to induce cervical cancer, knowledge of pathways that link the latent stage of the viral replication cycle to precancerous and cancerous stages remains incomplete. However, it is interesting to note that the virus can be isolated from tissues ranging from normal to low-grade squamous intraepithelial lesions as well as high-grade intraepithelial lesions (HSILs), thus prompting scientists to develop HPV detection methods for screening. Detection of HPV using viral proteins such as L1 and E1 is proposed to be very useful in assisting the management of high risk infection and cervical cancer. These tests however can lead to false positive results, largely due to the exisstence of asymptomatic or transient HPV infections within any given individual. Somes observation indicate that use of HPV proteins such as E6 and E7 might lead to false positive results. However, one particular HPV protein, E4 shows potential as an accurate marker of the tissue state following HPV infection. E4 expression has been shown to correlate with the levels of HPV DNA incorporation by the host. Thus, it is possible that E4 could serve as a useful marker to define stages of viral carcinogenesis.

Solid-pseudopapillary carcinoma: a case study and literature review.

Solid-pseudopapillary tumour (SPT) is a rare exocrine tumour of the pancreas and is considered to have low malignant potential. Few morphological criteria are used to predict malignant behaviour such as equivocal perineural invasion, angioinvasion and invasion to surrounding tissue, and should be designated as solid-pseudopapillary carcinoma (SPC). We report a case of SPC. Clinical and radiological findings are typical for SPT with no metastatic disease. There is no tumour recurrence after 4 months postresection. Clinical history and radiological findings were retrieved from the patient's record sheet and Viarad system. H&E staining and few immunoproxidase staining were reviewed by several pathologists. The histological findings are typical for SPT, with additional perineural invasion. There is no angioinvasion or capsular invasion identified. This is our first experience in diagnosing and managing SPC. We look forward to seeing the patient's disease status during her next routine follow-up. We expect good disease-free survival and very low risk of tumour recurrence, in view of only one risk factor (perineural invasion) and uninvolved surgical margins by the tumour.