MATERIALS AND METHODS: In mutation screening of CRNN gene, gDNA from OSCC tissues were extracted, amplified, and followed by direct sequencing. OSCC samples were also subjected to fragment analysis on CRNN gene to investigate its microsatellite instability (MSI) and loss of heterozygosity (LOH). Immunohistochemistry was performed to validate CRNN downregulation in OSCC samples.
RESULTS: No pathogenic mutation was found in CRNN gene, while high frequency of allelic imbalances was found at 1q21.3 region. MSI was found more frequent (25.3 %) than LOH (9.3 %). Approximately 22.6 % of cases had high MSI which reflects higher probability of inactivation of DNA mismatch repair genes. MSI showed significant association with no betel quid chewing (p = 0.003) and tongue subsite (p = 0.026). LOH was associated with ethnicity (p = 0.008) and advanced staging (p = 0.039). The LOH at 1q21.3 was identified to be as an independent prognostic marker in OSCC (HRR = 7.15 (95 % CI, 1.41-36.25), p = 0.018). Downregulation of CRNN was found among MSI-positive OSCCs and was associated with poor prognosis (p = 0.044).
CONCLUSION: This study showed a significant correlation between LOH/MSI at 1q21.3 with clinical outcomes and that downregulation of CRNN gene could be considered as a prognostic marker of OSCC.
CLINICAL RELEVANCE: Insights of the downregulation mode of CRNN gene lays the basis of drug development on this gene as well as revealing its prognostic value.
METHODS: Sprague Dawley rats (n = 7, body weight = 300 g ± 50 g) were grouped randomly into two groups-control (n = 3) and expanded (n = 4). Anisotropic hydrogel tissue expanders were inserted into the frontal maxillofacial region of the rats in the expanded group. The rats were sacrificed, and skin samples were harvested, fixed in formalin, and embedded in paraffin wax for histological investigation. Hematoxylin and eosin staining was performed to detect histological changes between the two groups and to investigate the inflammatory response in the expanded samples. Three inflammatory markers, namely interleukin (IL)-1α, IL-6, and tumor necrosis factor-α (TNF-α), were analyzed by immunohistochemistry.
RESULT: IL-1-α expression was only observed in the expanded tissue samples compared to the controls. In contrast, there was no significant difference in IL-6, and TNF-α production. Histological analysis showed the absence of inflammatory response in expanded tissues, and a negative non-significant correlation (Spearman's correlation coefficient) between IL-1-α immune-positive cells and the inflammatory cells (r = -0.500). In conclusion, tissues that are expanded and stabilized using an anisotropic self-inflating hydrogel tissue expander might be useful for tissue replacement and engraftment as the expanded tissue does not show any sign of inflammatory responses. Detection of IL-1-α in the expanded tissues warrants further investigation for its involvement without any visible inflammatory response.
Case presentation: A 26-year-old lady presented with anterior neck swelling with symptoms of superior vena cava syndrome for 6 months. Imaging study revealed a mediastinal mass which was preceded with core biopsy which was consistent with high-grade small cell NETs. Despite second-line adjuvant chemotherapy and radiotherapy, her disease became advanced which was confirmed via restaging scan. There were bilateral breast lesions discovered during the scan which was deemed to be metastatic NETs histologically. Despite prompt initiation of treatment, she succumbed 1 year after the radiotherapy due to disease progression.
Conclusion: High suspicion of an index is needed for diagnosis when patients with known primary NETs present with suspicious breast lesions. Triple assessment is mandatory, however histopathology assessment and immunohistochemistry staining are the mainstay of diagnosis.
Materials and Methods: We examined RANKL expression in 39 patients (21 males, 18 females) by immunohistochemistry. Four patients (10%) were presented with tumor recurrence, eight patients (20%) were complicated with lung metastasis, and two patients (5%) were presented with both recurrence and lung metastasis. Positive RANKL expression was assessed according to a scoring system evaluating the percentage of the immunostained epithelial area and the staining intensity. The cumulative score was calculated to determine the final score value. Data were analyzed using PASW version 18.0 and independent t-test between nonrecurrence/recurrence groups, and nonlung metastasis/lung metastasis groups. Significance was set at P < 0.05.
Results: Thirty-two patients (82%) scored 3 in RANKL-staining percentage from whole stromal cell population (>75%), 6 patients scored 2, and 1 patient scored 1. Nine patients (23%) scored 3 in RANKL-staining intensity (most intense), 19 patients (48%) scored 2, and 11 patients (29%) scored 1. Twenty six patients (67%) had strong RANKL expression (total score of 5-6), 12 patients (31%) showed moderate score (3-4) whereas only 1 patient (2%) showed weak RANKL expression. Together, the mean value of RANKL-staining percentage was 2.79, intensity 1.95 and the total score 4.77. The mean RANKL-staining percentage between recurrence and nonrecurrence groups was statistically significant (P = 0.009). There was no significant difference in the mean staining intensity and total score between nonrecurrence and recurrence groups, and staining percentage staining intensity and a total cumulative score of RANKL expression between lung metastasis and nonlung metastasis groups.
Conclusion: RANKL expression is generally high in Stage III GCT and is a reliable prognostic marker in predicting the risk of local recurrence however not in lung metastasis.
Materials and Methods: Five treatment groups were established as follows: Group 1 (C), which was given distilled water; Group 2 (T0), which was administered with LA (10 mg/kg body weight [BW]); and Groups 3 (T1), 4 (T2), and 5 (T3), which were given LA (10 mg/kg BW) plus graded concentrations of 30, 60, and 120 mg/kg BW of EBN, respectively. Rats were euthanized at week 5 to collect blood for superoxide dismutase (SOD) assay, and uterus for histomorphological study and expression analyses of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA).
Results: Results revealed that LA causes destruction of uterine lining cells and necrosis of uterine glands of exposed rats without EBN supplement while the degree of damage decreased among EBN treated groups; T3 showed the highest ameliorating effect against LA toxicity, as well as an increased number of uterine glands. Increased levels of SOD were also achieved in EBN supplemented groups than the controls. Results of immunohistochemistry showed significantly higher expressions of EGF, VEGF, and PCNA levels (p<0.05) in T3 compared to other treatments. EBN maintained upregulation of antioxidant - reactive oxygen species balance.
Conclusion: The findings showed that EBN could ameliorate the detrimental effects of LA toxicity on the uterus possibly by enhancing enzymatic antioxidant (SOD) activity as well as expressions of EGF, VEGF, and PCNA with cell proliferation roles.
MATERIALS AND METHODS: Thirty-six clear cell RCC cases were selected. There were 21 (58.3%) men and 15 (41.7%) women with median age of 56.6 years (range: 16-74 years). Chinese constituted 16 (44.4%) of the cases; Malays 14 (38.9%) cases and Indian 6 (16.7%) cases. There were 6 (16.7%) grade 1, 20 (55.6%) grade 2, 10 (27.8%) grade 3 and none was grade 4. The paraffin embedded tissues were cut at 4 μm thick and stained with COX-2 monoclonal antibody.
RESULTS: Eighteen (50%) of the RCC cases were immunopositive, of which all showed strong positivity. The immunopositive cases showed cytoplasmic membrane positivity.
CONCLUSION: There was no significant association between COX-2 expression with grade, age, sex and ethnicity (p=0.457, p=0.054, p=0.389 and p=0.568 respectively). Strong positivity of COX-2 suggest that COX-2 may play a role in cell proliferation and in carcinogenesis.
CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered.
DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.