Macrophage Inflammatory Proteins (MIPs) Contribute to Malignant Potential of Colorectal Polyps and Modulate Likelihood of Cancerization Associated with Standard Risk Factors.

Better understanding of molecular changes leading to neoplastic transformation is prerequisite to optimize risk assessment and chemopreventive and surveillance strategies. Data on macrophage inflammatory proteins (MIPs) in colorectal carcinogenesis are scanty and their clinical relevance remains unknown. Therefore, transcript and protein expression of CCL3, CCL4, CXCL2, and CCL19 were determined in 173 and 62 patients, respectively, using RT-qPCR and immunohistochemistry with reference to polyps' characteristics. The likelihood of malignancy was modeled using probit regression. With the increasing malignancy potential of hyperplastic-tubular-tubulo-villous-villous polyps, the expression of CCL3, CCL4, and CCL19 in lesions decreased. CCL19 expression decreased also in normal mucosa while that of CXCL2 increased. Likewise, lesion CCL3 and lesion and normal mucosa CCL19 decreased and normal CXCL2 increased along the hyperplasia-low-high dysplasia grade. The bigger the lesion, the lower CCL3 and higher CXCL2 in normal mucosa. Singular polyps had higher CCL3, CCL4, and CCL19 levels in normal mucosa. CCL3, CCL4 and CXCL2 modulated the likelihood of malignancy associated with traditional risk factors. There was no correlation between the protein and mRNA expression of CCL3 and CCL19. In summary, the polyp-adjacent mucosa contributes to gaining potential for malignancy by polyps. MIPs may help in specifying cancerization probability estimated based on standard risk factors.

Safety, feasibility, and effectiveness of a CT-guided transthoracic lung and pleural biopsy - a single-centre experience with own low-dose protocol.

Purpose: To assess the efficacy and safety of a low-dose, computed tomography (CT)-guided transthoracic biopsy of lung and pleural lesions. Material and methods: A total of 135 low-dose, CT-guided transthoracic lung and pleural lesions biopsies were performed. A cutting needle was utilized in 124 cases, and fine needle aspiration biopsy was performed in 14 cases. In all cases, 14- to 22-gauge biopsy needles were used. Results: Diagnostic material was obtained in 111 (82.2%) patients. In 97 (71.8%) cases neoplastic lesions were found, predominantly adenocarcinoma and non-small cell carcinoma. In 14 (12.6%) cases non atypical cells were reported. Biopsy failed to obtain material suitable for histopathological examination in 24 (17.7%) cases. Complications occurred in 31 patients, including pneumothorax in 28 patients and haematoma in 3 cases. Conclusions: Based on the obtained results, it can be stated that low-dose, CT-guided transthoracic biopsy of lung and pleural tissues is an accurate and safe procedure. Also, it is linked to a low risk of complications such as a small pneumothorax.

Comparison of the ICC location in the gallbladder wall in patients with cholelithiasis and patients with non-calculous changes.

Interstitial cells of Cajal (ICC) were first described by Santiago Ramon y Cajal over 100 years ago. They are thought to play an important role in the regulation of gastrointestinal motility. There is increasing evidence that the decline in their number in the gallbladder wall contributes to the formation of concrements. The aim of the study was to determine the exact location of interstitial cells of Cajal in the gallbladder wall in patients with calculous and non-calculous cholecystitis. Sixty-eight patients were examined, of whom 50 were cases of cholelithiasis and 18 were of non-calculous cholecystitis. The technique of immunohistochemistry with the CD117 antibody was used to determine the cells of Cajal, while to distinguish them from mast cells the technique with mast cell tryptase (MCT) was applied. Redistribution of the interstitial cells of Cajal from the muscle membrane to lamina propria of mucous tissue was observed in the cases of cholelithiasis, while in the group of non-calculous cholecystitis most of the ICC was located within the muscle tissue.

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

The variety of clinical presentations in IgG4-related disease in Rheumatology.

IgG4-related disease (IgG4-RD) belongs to the group of rare diseases in which the identification of the characteristic histology and immunohistochemistry provides with the gold standard in the diagnosis. The variable organ dysfunction reflects the clinical presentation. The examples of different IgG4-RD presentations in the Rheumatology Unit were discussed in this article. The spectrum of IgG4-RD is wide-ranging and manifested in one or more organs synchronously or metachronously. In the presented article, we described five different cases of IgG4-RD. Four cases were reaffirmed in the histopathological assessment. The clinical and laboratory findings were analyzed and the assigned therapy was discussed. According to our experience, the diagnosis of IgG4-RD requires the careful clinicopathological correlation. The diagnosis relies on the coexistence of various clinical, laboratory, radiological, and histopathological findings, although none of them is pathognomonic itself. The time needed for the diagnosis and variety of clinical forms of IgG4-RD shows that there is need of the cooperation among many specialists for the better and earlier recognition of the disease.

Polo-like kinase-1 immunoreactivity is associated with metastases in cutaneous melanoma.

BACKGROUND: Polo-like kinase-1 (PLK-1) is one of the key regulators of cell cycle progression. Increased expression of PLK-1 was observed in several tumor types. METHODS: We immunohistochemically assessed PLK-1 expression in neoplastic and stromal compartments of 96 cutaneous melanomas, and analyzed associations between PLK-1 expression and clinicopathological characteristics. RESULTS: PLK-1 expression in cancer cells was not associated with basic clinical (eg, age, gender and tumor location) or histopathological (eg, Breslow thickness, mitotic rate and ulceration) parameters. However, increased PLK-1 was more frequent in tumors with concurrent regional nodal metastases and positive sentinel lymph node biopsy status. All primary tumors associated with co-existing distant metastases exhibited high PLK-1 expression in melanoma cells. Conversely, PLK-1 expression in stromal cells was more frequent in tumors without nodal metastases. PLK-1 expression in both compartments was not associated with survival. CONCLUSION: PLK-1 expression is associated with metastatic potential in cutaneous melanoma.

The prognostic value of fine-needle aspiration biopsy of the thyroid gland - analysis of results of 1078 patients.

OBJECTIVE: We aimed to evaluate the prognostic value of thyroid fine needle aspiration biopsy (FNAB) in the diagnosis of pathologic lesions. METHODS: Data from 1 078 consecutive patients (female : male ratio, 9:1) who underwent thyroidectomy were retrospectively analyzed. All patients had preoperative thyroid FNAB. Unilateral and bilateral FNAB were performed in 872 and 206 patients, respectively, resulting in 1 284 cytologic aspirates, which were compared to postoperative histology. Risk factors for malignancy (age, sex, single nodule, or nodule in multinodular goiter) were evaluated. RESULTS: 203 (15.81%) aspirates were non-diagnostic. 768 (59.81%) were benign; 112 (8.72%) were atypical; 170 (13.24%) were follicular neoplasms, 5 (0.4%) had suspicion of malignancy; and 26 (2.02%) were malignant tumors on FNAB. The calculated risk of malignancy in each group was: 1.97%, 1.84%, 7.15%, 12.35%, 60%, and 100%. There were 2.02% false negative and 0.15% false positive results. Diagnostic discrepancies occurred in the follicular neoplasm group, of 86 biopsies (0.15%). CONCLUSION: FNAB is the primary method of preoperative diagnostics of thyroid tumors, as it allows many patients to avoid thyroidectomy. In addition, it helps the operating surgeon to decide the extent of surgical resection.

Inter- and intraobserver agreement in whole-slide digital ThinPrep samples of low-grade squamous lesions of the cervix uteri with known high-risk HPV status: A multicentric international study.

BACKGROUND: High-risk human papilloma virus (HR HPV) testing and liquid-based cytology are used for primary cervical screening. Digital cytology, based on whole-slide scanned samples, is a promising technique for teaching and diagnostic purposes. The aim of our study was to evaluate the interobserver and intraobserver variation in low-grade squamous lesions, HR HPV status bias, and the use of whole-slide scanned digital cervical cytology slides. METHODS: Fifteen expert cytopathologists evaluated 71 digitalized ThinPrep slides (31 atypical squamous cells of undetermined significance [ASC-US], 21 negative for intraepithelial lesion or malignancy, and 19 low-grade squamous intraepithelial lesion cases). HR HPV data were accessible only in the second round. RESULTS: In interobserver analysis, Kendall's coefficient of concordance was 0.52 in the first round and 0.58 in the second round. Fleiss' kappa values were 0.29 in the first round and 0.31 in the second round. In the ASC-US category, Fleiss kappa increased from 0.19 to 0.22 in the second round and the increase was even higher expressed by Kendall's coefficient: from 0.42 to 0.52. In intraobserver analysis, personal scores were higher in the second round. CONCLUSIONS: The interobserver and intraobserver variability in low-grade squamous lesions was within fair agreement values in the present study, in line with previous works. The comparison of two rounds showed that expert cytopathologists are generally unbiased by the knowledge of HR HPV data, but that being informed of the HR HPV status leads to a better agreement. Stain quality and back discomfort were highlighted as factors affecting digital cytopathology use.

Monocyte Chemotactic Proteins (MCP) in Colorectal Adenomas Are Differently Expressed at the Transcriptional and Protein Levels: Implications for Colorectal Cancer Prevention.

The expression of monocyte chemotactic proteins (MCPs) in colorectal polyps and their suitability as targets for chemoprevention is unknown, although MCP expression and secretion can be modulated by non-steroidal inflammatory drugs. This study was designed to determine the expression patterns of MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 at the protein (immunohistochemistry; n = 62) and transcriptional levels (RTqPCR; n = 173) in colorectal polyps with reference to the polyp malignancy potential. All chemokines were significantly upregulated in polyps at the protein level but downregulated at the transcriptional level by 1.4-(CCL2), 1.7-(CCL7), and 2.3-fold (CCL8). There was an inverse relation between the immunoreactivity toward chemokine proteins and the number of corresponding transcripts in polyps (CCL2 and CCL7) or in normal mucosa (CCL8). The downregulation of chemokine transcripts correlated with the presence of multiple polyps (CCL2 and CCL8), a larger polyp size (CCL2, CCL7, and CCL8), predominant villous growth patterns (CCL2, CCL7 and CCL8), and high-grade dysplasia (CCL2 and CCL8). In conclusion, MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 chemokines are counter-regulated at the protein and transcriptional levels. Chemokine-directed chemopreventive strategies should therefore directly neutralize MCP proteins or target molecular pathways contributing to their enhanced translation or reduced degradation, rather than aiming at CCL2, CCL7 or CCL8 expression.

ARID1A/BAF250a is significantly overexpressed in primary invasive breast cancer.

BACKGROUND: ARID1A (also known as BAF250a, p270 or SMARCF1) is a major component of the mammalian SWI/SNF family that is involved in the regulation of the chromatin structure. ARID1A gene mutations have been associated with many types of malignancies, including breast cancer. This study aimed to explore the expression of BAF250a protein in breast cancer and its association with the clinical and pathological characteristics and prognosis of breast cancer. METHODS: We assessed the BAF250a expression in 119 invasive breast carcinomas samples and 92 healthy control and correlated this expression pattern with various clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor (ER) status, progesterone receptor (PR) status. Immunohistochemical analysis of BAF250a, ER, PR, was carried out, and evaluation of stainings was performed. RESULTS: The mean value of BAF250a expression in the experimental group was higher than in healthy control (P=0.001). The expression is unrelated to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (ER, PR). CONCLUSIONS: These data suggest that BAF250a is overexpressed in breast cancers. BAF250a may play context-dependent tumor-promoting and tumor-suppressive roles in cancer.

Using photodynamic therapy to estimate effectiveness of innovative combined diclofenac and tazaroten therapy of disseminated actinic keratosis.

Early diagnosis and therapy of precancerous lesions and malignant tumors belong to the most challenging tasks in modern medicine. Photodynamic diagnosis can help diagnose both precancerous lesions and early carcinoma. Actinic keratosis (AK) is the most common precancerous lesion of the skin. The available data show a high effectiveness of diclofenac in treating multifocal AK. We report a case of a 52-year-old woman who complained of multiple disseminated AK lesions predominantly on the lower limbs and trunk with a significant exacerbation within the last 6 months. Due to the spreading of disease and a high number of AK foci, as well as technical problems with visiting the hospital (PDT Laboratory), photodynamic therapy was not applied. The patient was treated for 2 months with a combination of local administration of 3% diclofenac and 0.1% tazaroten and 3% diclofenac only as a half side (left-right) comparison. The effects of therapy were later clinically evaluated and verified by means of photodynamic diagnosis (PDD) directly after therapy and at a follow-up examination 3 months later. The evaluation of treatment was blinded. Treatment with diclofenac only on the right side of the body resulted in clearing of 55% of all treated lesions, which increased to 60% three months after finishing therapy. On the left side of the body, where combined therapy (diclofenac 2 times daily on uneven dates and diclofenac once a day + tazaroten once a day on even dates) was used, 77.5% pathologic lesions disappeared, but this did not increase at follow up. The treatment of multifocal, disseminated AK is a difficult task and also burdensome for the patient due to side effects like scarring or burning and itching which occur during most therapies. Combined therapy with diclofenac and tazaroten supported by PDD may improve the effects of routine treatment of AK.

Morphometry in the cytological diagnosis of cervical smears.

BACKGROUND: Morphometry of cells found in normal and abnormal smears taken from the vagina and the uterine cervix is the assessment of the size and diameter of their nuclei. The values of these quantities provide information on the origin of these cells and the degree of possible anomalies. Determining the morphometric traits of different types of cells found in the cervix and the uterus is a very important element in the diagnosis of disorders that often lead to cervical tumors. OBJECTIVES: The aim of this research is to determine the morphometric characteristics of cells found in cervical smears by measuring the cell circumference, the diameter of the nucleus and the cell surface areain order to identify which clinical group the cells belong to, which facilitates diagnosis. MATERIAL AND METHODS: The study material consisted of cervical smears that demonstrated the presence of cells in various phases of the clinical Bethesda classification. For each clinical classification, the values of the cell circumference, the cell surface area and the diameter of the nucleus were measured for 100 cells. RESULTS: The largest cells are normal cells in the surface layer. In relation to these cells, the atrophic cells from the groups containing atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesion (HSIL) and tumor cells tend to decrease in size, with small variations. Considering the mean values of the parameters analyzed, the cells of the LSIL group are larger than those from the ASC-US group. According to the mean values, normal cells have the smallest nucleus and the HSIL cells and tumor cells have the largest. CONCLUSIONS: The statistical analysis shows significant differences between the morphometric traits in the different clinical groups, which indicates that morphometry can be used in cytological diagnosis.