Keratin 20 - a diagnostic and prognostic marker in colorectal cancer?

Colorectal cancer cells characteristically show strong expression of keratin 20 (K20) and lack expression of keratin 7 (K7). The biological significance of reduced K20 expression, however, is unclear. 381 colorectal cancers with 148 corresponding metastases were evaluated for K20 and K7 expression by immunohistochemistry using a tissue microarray technique. K20 immunoreactivity was assessed semiquantitatively as either negative, low (<50% of cancer cells) or high (≥50% of cancer cells). Progression-free and cancer-specific survivals were determined using the Kaplan-Meier method. Expression of K20 was observed in 348 out of 372 (94%) evaluable primary tumors, with 135 (36%) cases showing low K20 and 213 (57%) cases high K20 expression, while 24 (6%) tumors completely lacked K20 immunoreactivity. Reduced K20 expression (lack of staining or low expression) was significantly associated with poor differentiation, large tumor size and mismatch repair deficiency, but did not significantly affect patients' outcome. Immunoreactivity of K20 and K7 in metastatic tissues matched well with that of corresponding primary tumors, with high concordance for lymph node (p<0.001) and distant metastases (p<0.001), respectively. In conclusion, our data illustrate the value of keratin subtyping in carcinoma of unknown primary (CUP) syndrome: K20 expression is common in colorectal cancer and the K20 high / K7 negative immunoprofile represents the predominant phenotype. Reduced K20 expression may, however, lead to false-negative assessment of metastatic deposits if only small amounts of tissue are obtained (e.g. in needle biopsies), particularly in poorly differentiated cancers. Reduced expression of K20 may be used to select tumors for microsatellite instability testing.     

Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.     

Neoadjuvant checkpoint inhibition in non-small cell lung cancer: Is earlier unquestionably better than later?

On March 4th 2022, nivolumab received regular US Food and Drug Administration approval, based on the CheckMate 816 trial results, for use “with platinum-doublet chemotherapy for adult patients with resectable NSCLC in the neoadjuvant setting”. This is the first neoadjuvant approval of a checkpoint inhibitor, a unique event in the history of lung cancer treatment. However, open questions remains. First, the co-primary endpoints of the CheckMate 816 trial (event-free survival and pathological complete response) are not yet validated surrogate endpoints in this setting. Second, the control arm was not reflecting the most common approach, being upfront surgery followed by adjuvant chemotherapy. Third, protocol changes were not plainly justified, questioning the analytic plan of the trial. Fourth and last, a subpar access to checkpoint inhibitor for patients upon progression may weaken overall survival results. Neoadjuvant strategies allow to study initial response under treatment, and constitute an encouraging therapeutic avenue. However, the best sequence of treatment is the key question in the neoadjuvant or adjuvant settings: is treating everyone upfront better than treating only patients that will eventually recur?Investigating optimal sequence strategy is even more critical within the checkpoint-inhibitor era, where patients with advanced or metastatic disease may present long-term advantage. Trials with optimal post-progression treatment are needed to help optimize our treatment algorithm, and spare toxicity for patients who don't derive benefit.     

Is the self always better than a friend? Self-face recognition in Christians and atheists

Early behavioral studies found that human adults responded faster to their own faces than faces of familiar others or strangers, a finding referred to as self-face advantage. Recent research suggests that the self-face advantage is mediated by implicit positive association with the self and is influenced by sociocultural experience. The current study investigated whether and how Christian belief and practice affect the processing of self-face in a Chinese population. Christian and Atheist participants were recruited for an implicit association test (IAT) in Experiment 1 and a face-owner identification task in Experiment 2. Experiment 1 found that atheists responded faster to self-face when it shared the same response key with positive compared to negative trait adjectives. This IAT effect, however, was significantly reduced in Christians. Experiment 2 found that atheists responded faster to self-face compared to a friend's face, but this self-face advantage was significantly reduced in Christians. Hierarchical regression analyses further showed that the IAT effect positively predicted self-face advantage in atheists but not in Christians. Our findings suggest that Christian belief and practice may weaken implicit positive association with the self and thus decrease the advantage of the self over a friend during face recognition in the believers.     

Is chymotrypsin output a better diagnostic index than the measurement of chymotrypsin in random stool?

This study compares the diagnostic utility of fecal chymotrypsin (CT) output in timed stool collections and random stools using a new photometric enzyme assay. The CT output (mean +/- SD, U/24 h) was 1,487 +/- 1,980 in 127 children with normal fat absorption and negative sweat-chloride test (mean age 45 months), and 1,804 +/- 1,452 in 27 cases with fat malabsorption due to nonpancreatic disease (mean age 41 months). 66 cases of cystic fibrosis (CF) were examined (mean age 119 months). Stool output in 19 newly diagnosed patients before therapy was 85 +/- 94, in 42 patients receiving enzyme replacement therapy was 3,462 +/- 2,841, and in 5 patients with pancreatic sufficiency 1,754 +/- 1,482. Using nonparametric statistics, 120 U/24 h was defined as the lower limit of the 95-percentile for stool CT output. Only 5 of the 127 patients with normal fat absorption had output below that limit. None of the patients with nonpancreatic malabsorption and only 1 treated CF patient had lower values. Sixteen of the newly diagnosed CF patients had stool CT less than 120 U/24 h. The sensitivity of the test is therefore 84% and its specificity 97% at this decision threshold. However, no diagnostic advantage is gained from measuring CT output in timed stool collections as compared to random stools.     

Is it possible to define a better ASCUS class in cervicovaginal screening? A review of 187 cases

OBJECTIVE: To try to better define the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) in a cervical screening protocol. STUDY DESIGN: Smears from 187 patients with cytologic diagnoses of ASCUS and histologic or two years' cytologic/colposcopic follow-up were reviewed. When an ASCUS diagnosis was confirmed, it was done strictly on the basis of the morphologic criteria recommended by the Regione Emilia Romagna Screening Protocol in 1997, trying also to subclassify ASCUS into favor reactive or favor neoplasia. RESULTS: Seventy ASCUS cases were negative (37.4%). Three cases (1.6%) were low grade squamous intraepithelial lesion, and seven (3.8%) were high grade squamous intraepithelial lesion. One hundred seven ASCUS cases (57.2%) were confirmed. Among the 70 negative cases, 36 (51.4%) had reactive changes on biopsy, 30 (42.9%) koilocytosis, 3 cervical intraepithelial neoplasia (CIN 1) and one CIN not otherwise specified (5.7% total). CONCLUSION: Reclassification of ASCUS cases using tighter criteria reduced them to a rate of 57.2% but missed 30 patients with histologic diagnoses of koilocytosis and 4 with histologic diagnoses of CIN.     

Is colorectal cancer a more aggressive disease in young patients? A population-based study from the Czech Republic

IntroductionThe incidence of colorectal cancer in young patients is increasing. The goal of this study was to investigate whether clinicopathological features and survival differed between young, middle-aged and elderly patients.MethodsThe Czech National Cancer Registry was searched to identify all cases of colorectal cancer between 1982 and 2014. Three subgroups of patients were created: young patients, defined as being between 18 and 40 years of age, middle-aged patients, defined as being between 41 and 74 years of age, and elderly patients, defined as being over the age of 75 years.ResultsA total of 192,241 patients diagnosed with colorectal cancer between the years 1982 and 2014 were included in the study. Out of these, 3,287 patients (1.7%) were between 18 and 40 years of age, 134,139 patients (69.8%) were between 41 and 74 years of age and 54,815 patients (28.5%) were 75 years of age or older. The young patients had a higher incidence of mucinous adenocarcinoma and signet ring cell carcinoma, more advanced disease and more rectal tumours than elderly patients. Nonetheless, young patients received treatment more frequently and had better cancer-specific survival than the older patients.ConclusionThe better prognosis in young patients is presumably due to their better physiological reserve and lower incidence of comorbidities. Efforts should be made in younger patients to diagnose early and treat aggressively.     

Is SNOLL a good localization technique in early breast cancer treatment? A single center’s experience

AimThe aim of this study was to evaluate the method and present one center’s experience in applying the SNOLL technique to patients with non-palpable suspicious breast lesions.Materials and methods371 patients with suspected malignant lesions or diagnosed non-palpable breast cancer were subjected to a preoperative SNOLL procedure. The day before the surgery, they were administered two radiotracers to localize the tumor in the breast and the sentinel node. The following day, with the help of a handheld gamma probe the breast conserving surgery was performed.ResultsAll 371 patients (100%) had their suspected occult breast lesions resected. Histo-pathological examination revealed cancer in 339 patients all these patients had their sentinel nodes examined. The intraoperative tests showed the sentinel node to be metastatic in 35 patients, who were then given a simultaneous axillary lymphadenectomy. Another 7 patients were diagnosed with positive lymph nodes in the final pathology and had to undergo a second operation. Reoperations compelled by positive surgical margins were performed in 26 cases.ConclusionsSNOLL as a good technique of intraoperative localization, enables to remove a nonpalpable breast cancer together with sentinel lymph node in a single surgical procedure. It seems to be a optional method to be used in patients treated with breast conserving therapy.     

Is there a relation between genetic susceptibility with cancer? A study about paraoxanase (PON1) enzyme activity in breast cancer cases

Human serum paraoxonase 1 (PON1, EC 3.1.1.2) is a high density lipoprotein (HDL)-associated antioxidant enzyme that not only decreases oxidative stress, but it is also implicated in development of many cancers. Genetic information provides a means of identifying people who have an increased risk of cancer, thus this knowledge of cancer genetics helps to identify the ability to characterize malignancies leading to the development of new therapeutic approaches. Because of this reason, in this preliminary study we aimed to investigate the role of human serum PON1 enzyme activity and phenotypic distribution in 32 breast cancer (BC) patients (age range 28–82) and 35 cancer free (CF) control group (age range 21–67). PON1 enzyme was prepared from the serum pool of BC patients using hydrophobic interaction chromatography on L-tyrosine-9-aminophenanthrene-coupled Sepharose 4Bgel. The PON1 enzyme activity towards paraoxon substrate was quantified spectrophotometrically. The basal activity of PON1 was statistically decreased in cancer cases compared to the control group. In addition, individuals were classified according to phenotyping of human PON1 Q and R types. In the cohort of BC patients, an increase in the frequency of the PON homozygote Q (AA) genotype was observed (31% in the BC group versus 14% in the CF controls). The frequency of the PON heterozygote QR (AB) genotype was 34.5% in the patients with BC and 37% in the CF group. The same trend was observed in PON homozygote R (BB) genotype frequency (BC cases 34.5% versus controls 49%). We determined that the kinetic parameters of the purified enzyme by Lineweaver–Burk method. We obtained K_m and V_max values of 0.227?mM and 62?U/mL?min for the BC enzyme, compared with 0.775?mM and 206?U/mL?min for the CF control enzyme. As a conclusion, it is clear from our results that while the PON1 AA allele frequency in BC cases is much higher, that of BB allele is much lower, in comparison with the control group. The most significant finding of this study is AA allele activity which is low in BC cases was found high. We concluded that decreased AA allele PON1 activity might have a relation with BC.     

Is quality more important than quantity? Insect behavioural responses to changes in a volatile blend after stemborer oviposition on an African grass

Plants subjected to insect attack usually increase volatile emission which attracts natural enemies and repels further herbivore colonization. Less is known about the capacity of herbivores to suppress volatiles and the multitrophic consequences thereof. In our study, the African forage grass, Brachiaria brizantha, was exposed to ovipositing spotted stemborer, Chilo partellus, moths. A marked reduction in emission of the main volatile, (Z)-3-hexenyl acetate (Z3HA), occurred following oviposition but the ratio of certain other minor component volatiles to Z3HA was increased. While further herbivore colonization was reduced on plants after oviposition, the new volatile profile caused increased attraction of an adapted parasitoid, Cotesia sesamiae. Our results show that insect responses are dependent on the quality of volatile emission rather than merely the quantity in this multitrophic interaction.     

Impact of polyunsaturated fatty acids on hepato-pancreatic prostaglandin and leukotriene concentration in ductal pancreatic cancer—Is there a correlation to tumour growth and liver metastasis?

Type and composition of polyunsaturated fatty acids (PUFAs) are suspected to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 PUFAs on tumour growth, liver metastasis and concentration of prostaglandins (PG) and leukotrienes (LT) in experimental ductal pancreatic adenocarcinoma. Ninety male hamsters were randomised into six groups (Gr.) (n=15). While Gr. 1-3 were healthy control groups, Gr. 4-6 weekly received subcutaneous injections of 10mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1 and 16 all animals were fed with a standard diet with a raw fat content of 2.9%. In week 17 Gr. 1-6 were allocated to three types of diets: Gr. 1: standard high fat (=SHF diet, rich in n-6 PUFAs)/Gr. 2: FISH-OIL (rich in n-3 PUFAs)/Gr. 3: SMOF (=mixture of n-3, n-6 and n-9 PUFAs)/Gr. 4: BOP+SHF/Gr. 5: BOP+SMOF/Gr. 6: BOP+FISH-OIL. After 32 weeks all animals were sacrificed and pancreas as well as liver were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1alpha, PGE(2)) and LT were measured. FISH-OIL decreased number of macroscopically visible pancreatic tumours (Gr. 4-6: 54.5% vs. 45.5% vs. 9.1%, P<0.05) as well as incidence of liver metastasis (Gr. 4-6: 90.9% vs. 72.7% vs. 36.4%, P<0.05). Furthermore concentration of PGF(1)(alpha), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1)(alpha) and PGE(2) were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of LT was significantly lower than in non-metastatic hepatic tissue as well as in Gr. 4 and Gr. 5. FISH-OIL decreased number of visible pancreatic tumours and incidence of histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of LT compared to extrametastatic hepatic tissue.