Prelude to malignancy: A gene expression signature in normal mammary gland from breast cancer patients suggests pre-tumorous alterations and is associated with adverse outcomes.

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

High tumour-infiltrating lymphocytes correlate with distinct gene expression profile and favourable survival in single hormone receptor-positive breast cancer.

Introduction: This study aimed to evaluate the impact of tumour-infiltrating lymphocytes (TILs) on the expression of immune-related genes and prognosis in single hormone receptor-positive breast cancer. Material and methods: Tumour-infiltrating lymphocytes were analysed according to the guidelines of the International TILs Working Group in a cohort of 206 patients with single hormone receptor-positive breast cancer. Of these, 44.7% were classified as ER+/PgR-/HER2-, 18.4% as ER+/PgR-/HER2+, 26.2% as ER-/PgR+/HER2-, and 10.7% as ER-/PgR+/HER2+. Moreover, in 52 samples the analysis of gene expression profiling was performed using nCounter technology. Results: Most cases (74.3%) showed at least 1% of stromal TILs, with a median of 4%, mean of 16.3%, and interquartile range of 0-20%. ER-/PgR+ tumours displayed significantly higher TILs density than ER+/PgR- cases (p < 0.001, Wilcoxon test), regardless of HER2 status. The abundance of TILs was positively associated with ER-/PgR+ phenotype, higher Ki-67, and higher grade, but not with age, tumour size, or regional and distant metastases at diagnosis. Additionally, in ER+/PgR- subgroup higher TILs were associated with HER2-positive status. Stromal TILs > 5% were associated with better survival in the whole group, but this effect was less prominent in ER-/PgR+ patients. We identified 50 differentially expressed genes (DEGs) between single hormone receptor-positive breast tumours with high and low TILs, including 39 up-regulated and 11 down-regulated genes in the high TILs group. Conclusions: The up-regulated expression of immune-related genes was consistent also among separately analysed single hormone receptor-positive groups (ER+/PgR- and ER-/PgR+).

Metastasis to the ureter as the first manifestation of occult pulmonary adenocarcinoma. Case report and review of the literature.

Lung cancer is a major epidemiological threat worldwide, which commonly metastasizes to distant sites. Often, the presence of metastasis is the first manifestation of lung cancer. Some of the most common sites for lung cancer metastasis are bones, adrenal glands, liver, brain, and lungs. However, metastases to unusual locations pose a diagnostic and therapeutic challenge. We present a case of a 74-year-old woman in whom the first manifestation of lung cancer was metastasis to the right ureter. We also analyse the available literature on lung cancer metastases to the ureter, taking into account the possible mechanisms of their spread in the ureter.

Galectin-9 expression on tumour-associated immune cells is associated with favourable clinicopathological features and better outcomes in oral squamous cell carcinoma.

Introduction: Galectin-9, a ß-galactoside-binding protein, might be a potential target in cancer personalized therapy, but contradicting data exist regarding its prognostic significance in malignancy. Previous studies showed low or absent expression of galectin-9 on tumour cells of oral squamous cell carcinoma (OSCC); thus, we aimed to assess the prognostic impact of its expression on tumour-associated immune cells (TAICs). Material and methods: A retrospective analysis was conducted on 62 patients with OSCC. Tissue microarrays were constructed with chemo- and radiotherapy-naïve tissue samples and stained with anti-galectin-9 antibody. Cytoplasmic reactions in TAICs were counted as positive, and the percentage of galectin-9-positive cells was calculated. Results: The expression of galectin-9 was not associated with any demographic factors, other than diabetes mellitus type 2, for which there were lower levels of expression (p = 0.029). Higher levels of galectin-9 were associated with less locally advanced tumours (p = 0.023) and lack of nodal metastases (p = 0.014). Galectin-9 expression positively correlated with PD-L1 expression on TAICs (p = 0.009). Patients with > 50% galectin-9-positive cells were determined to have a superior 5-year overall survival (p = 0.029). Conclusions: Future studies are necessary to investigate the effects of galectin-9 on the tumour micro-environment, and galectin-9-targeted treatment may be considered, especially with its correlation to PD-L1 in OSCC.

Alterations in key signaling pathways in sinonasal tract melanoma. A molecular genetics and immunohistochemical study of 90 cases and comprehensive review of the literature.

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas.

Diagnostically misleading aberrant terminal deoxynucleotidyl transferase expression in germ cell tumors.

Terminal deoxynucleotidyl transferase (TdT) is a unique type of DNA polymerase predominantly expressed in precursor lymphoid cells and acute lymphoblastic leukemia. It participates in the junctional diversity of T-cell receptors and immunoglobulins. Recently, aberrant TdT expression was found in seminomas. Here, we evaluated the expression of TdT in our cohort of germ cell tumors (GCTs) with two anti-TdT antibody clones. We included 173 cases of testicular GCTs, 5 ovarian dysgerminomas, and one gonadoblastoma in the study. Tissue microarrays containing representative tumor samples were constructed and subsequently stained with anti-TdT monoclonal rabbit antibody EP266 (Dako) and TdT rabbit polyclonal antibody (Cell Marque). Expression was assessed with the H-score. No specific nuclear reaction was observed for the polyclonal anti-TdT antibody. The H-score values varied between the histological subtypes for the EP266 antibody. Positive nuclear staining was consistently seen in germ cell neoplasia in situ , seminoma, dysgerminoma, and embryonal carcinoma. Pure tumors had higher TdT H-scores than the mixed ones. Teratomas, yolk sac tumors, and choriocarcinomas were almost uniformly negative. Our study confirms that aberrant expression of TdT by testicular and ovarian GCTs exemplifies a potential diagnostic pitfall in histopathological diagnostics.

The B7 family molecules in oral squamous cell carcinoma: a systematic review. Part I: B7-H1 (PD-L1) and B7-DC (PD-L2).

Introduction: Oral squamous cell carcinoma (OSCC) is the most common cancerous lesion in the oral cavity. During recent years, no significant reduction in the survival rate has been observed. Aim: To systematically review the literature and to summarise correlations between B7 family proteins and prognosis in OSCC. Material and methods: A systematic review of the literature about B7-H1 (PD-L1) and B7-DC (PD-L2) was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Thirty-six articles published before 22 May 2020 were included in the systematic review. Results: The biggest study group consisted of 305 patients and the smallest - 10 patients. PD-L1 proved to be a prognostic factor in patients with OSCC. Immunohistochemistry was the most commonly used diagnostic method. Conclusions: Any mutations in the gene encoding PD-L1 and quantitative or functional changes in the status of PD-L1 may be important in the prognosis of OSCC.

Quantitative imaging of the receptor for advanced glycation end-products in prostate cancer.

PURPOSE: Current screening and monitoring of prostate cancer (PCa) is insufficient, producing inaccurate diagnoses. Presence of the receptor for advanced glycation end-products (RAGE) is associated with signature characteristics of PCa development such as cell proliferation, anchorage-independent growth, angiogenesis, migration, invasion, and poor patient survival. Therefore, we developed a preclinical multimodal imaging strategy targeted at RAGE to diagnose and monitor PCa. METHODS: In this work, RAGE-targeted multimodal nanoparticles (64Cu-Cy5-G4-CML) were synthesized and rendered functional for nuclear and optical imaging using previously established methods. The probe's binding affinity and targeting specificity was assessed in androgen-dependent (LNCaP) and androgen-independent (DU145) prostate cancer cells using flow cytometry and confocal microscopy. In vivo PET-CT imaging was used to evaluate RAGE levels in DU145 and LNCaP xenograft models in mice. Then, tumors were excised post-imaging for histological staining and autoradiography to further assess RAGE levels and targeting efficiency of the tracer. Finally, RAGE levels from human PCa samples of varying Gleason Scores were evaluated using Western blot and immunohistochemical staining. RESULTS: PCa cell culture studies confirmed adequate RAGE-targeting with 64Cu-Cy5-G4-CML with KD between 360 and 540 nM as measured by flow cytometry. In vivo PET-CT images of PCa xenografts revealed favorable kinetics, rapid blood clearance, and a non-homogenous, enhanced uptake in tumors, which varied based on cell type and tumor size with mean uptake between 0.5 and 1.4%ID/g. RAGE quantification of human samples confirmed increased RAGE uptake corresponding to increased Gleason scoring. CONCLUSIONS: Our study has shown that RAGE-targeted cancer imaging is feasible and could significantly impact PCa management.

Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.

HtrA proteases regulate cellular homeostasis and cell death. Their dysfunctions have been correlated with oncogenesis and response to therapeutic treatment. We investigated the relation between HtrA1-3 expression and clinicopathological, and survival data, as well as the microsatellite status of tumors. Sixty-five colorectal cancer patients were included in the study. The expression of HTRA1-3 was estimated at the mRNA and protein levels by quantitative PCR and immunoblotting. Microsatellite status was determined by high-resolution-melting PCR. We found that the HTRA1 mRNA level was higher in colorectal cancer tissue as compared to the unchanged mucosa, specifically in primary lesions of metastasizing cancer. The levels of HtrA1 and HtrA2 proteins were reduced in tumor tissue when compared to unchanged mucosa, specifically in primary lesions of metastasizing disease. Moreover, a decrease in HTRA1 and HTRA2 transcripts' levels in cancers with a high level of microsatellite instability compared to microsatellite stable ones has been observed. A low level of HtrA1 or/and HtrA2 in cancer tissue correlated with poorer patient survival. The expression of HTRA1 and HTRA2 changes during colorectal carcinogenesis and microsatellite instability may be, at least partially, associated with these changes. The alterations in the HTRA1/2 genes' expression are connected with metastatic potential of colorectal cancer and may affect patient survival.

Childhood longitudinal melanonychia: case series from Poland.

INTRODUCTION: Longitudinal melanonychia (LM) is characterized by a tan, brown or black longitudinal streak within nail plate caused by the presence of melanin. LM is relatively common in dark-skinned population, infrequent in Caucasian population, and rare in children. AIM: We report epidemiological, clinicopathological and dermoscopic analysis of 8 cases of childhood LM from Poland, which is the largest series in the Central and Eastern European population. MATERIAL AND METHODS: Three hundred and forty-eight patients presenting with various nail pigmentation (in 2010-2016) were analysed. 72 cases of LM have been identified, including 8 cases of childhood LM (< 16 years of age), which were included in further analysis. RESULTS: Seven patients were boys and one girl, with mean age of 9 years (range: 6-13). More than a half (n = 5) presented skin phototype II. The most common location of melanonychia was the first left fingernail. Dermoscopy revealed heterogeneity of longitudinal lines colour in 5 cases. The irregularity of longitudinal line thickness in 5 cases and irregularity of parallelism in 5 cases was observed. Histopathological evaluation was performed in 4 patients, in 3 cases it revealed the presence of nail matrix nevus, in one case the presence of melanocytic proliferation of the lentiginous pattern along the dermoepidermal junction. CONCLUSIONS: Despite the fact that melanoma was not recognised in any case, such a possibility should always be considered as the cause of LM, even in the paediatric population. Dermoscopy seems to be useful in patient follow-up and management.

Aromatase inhibitor therapy for endometrial stromal sarcoma - two-centre experience.

OBJECTIVES: Endocrine therapy is the recommended systemic treatment for steroid receptor positive endometrial stromal sarcoma (ESS). There is no current consensus on the optimal hormonal therapy for ESS. The literature offers several reports on advanced/recurrent/metastatic ESS patients treated with progestins, whereas data on the efficacy of aromatase inhibitors are scarce. MATERIAL AND METHODS: We retrospectively identified cases treated for ESS with aromatase inhibitors at our institutions. There were five patients with advanced or unresectable recurrent estrogen, progesterone and androgen receptor-positive ESS, treated with aromatase inhibitors: letrozole or anastrozole (at a daily dose of 2.5 mg and 1 mg, respectively), as first-line endocrine therapy in all but one case treated following progression with megestrol acetate. RESULTS: Disease stabilization was achieved in four cases (80%), including two with long-term progression-free survival for up to 10 years attained under letrozole treatment, and one case after prior progestin treatment. During therapy, no substantial toxicity was observed. CONCLUSIONS: Aromatase inhibitors as first- or second-line endocrine treatment achieve disease control in most steroid receptor positive ESS. Our series of cases is evidence of aromatase inhibitors efficacy as long-term endocrine treatment option for ESS patients.

Liver metastasis of a neuroendocrine neoplasm of unknown primary origin in a female patient with a history of breast cancer.

We report on and discuss a case of a female patient diagnosed with breast cancer in 1996, which was histopathologically assessed as an invasive ductal carcinoma. The patient was admitted to our Department in 2017 with a liver metastasis of a neuroendocrine tumour. On admission she had no symptoms of an endo-crinopathy and was in a good general condition. Due to unknown primary site of the metastasis and given the patient's history of breast cancer, it was suspected that the breast cancer was in fact a neuroendocrine tumour. This hypothesis was confirmed by comparing histopathological specimens of the breast and liver tumours using advanced pathological methods.

Diagnostic and prognostic role of SF1, IGF2, Ki67, p53, adiponectin, and leptin receptors in human adrenal cortical tumors.

BACKGROUND: The authors have examined the immunohistochemical expression of several proteins and their relationship with adrenal cortical carcinoma (ACC) diagnosis and progression. MATERIALS AND METHODS: A total of 83 patients with benign and malignant adrenal cortex tumors operated on in a single center were included in the study. Expression of the following proteins was examined: steroidogenic factor 1 (SF1), insulin growth factor 2 (IGF2), Ki67, p53, as well as adiponectin (Adipo R1, Adipo R2), and leptin (Ob-R) receptors. RESULTS: Multivariate analysis revealed that the expression of SF1, IGF2, and Adipo R1 and R2 receptors was associated with ACC diagnosis. An acknowledged proliferation marker Ki67 was related with the size of ACC and was an independent ACC diagnosis marker. The authors also assessed the relationship between immunohistochemical parameters and overall survival (OS) and disease progression. Only high IGF2 expression was associated with longer OS (P = 0.025). The most significant one for the prognosis of ACC patients was tumor resectability of the primary tumor. More favorable prognosis was found for young men (P = 0.033). CONCLUSIONS: The presented data indicate that immunohistochemical assessment (of IGF2, SF1, Adipo R1, and R2 receptors' expression) may be useful in making the diagnosis of uncertain ACC cases.

Self-diagnosis of hyperparathyroidism during pregnancy resulting in parathyroidectomy and uncomplicated delivery.

Primary hyperparathyroidism is a condition with hypercalcemia and elevated parathyroid hormone (PTH). Typically, treating patients with such disease does not pose a problem for doctors, unless the patient is pregnant. Firstly, pregnancy may mask signs of hypercalcemia. Secondly, treatment should be applied with special care for immature fetus. If undiagnosed and untreated, it is life-threatening for the mother and the baby. The main cause of primary hyperparathyroidism is parathyroid adenoma, which should be removed surgically in second trimester. If the patient is monitored by a multidisciplinary team, the risk of mortality and pregnancy loss is reduced.

The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis.

INTRODUCTION: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated, systemic disease characterized by necrotizing small and medium vessel vasculitis of unknown etiology associated with granulomatous inflammation affecting the renal, pulmonary, upper airways, ocular systems and other tissues. Histological proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of clinically involved sites. The main purpose of this study was to examine histopathological changes in non-renal biopsies from patients with established diagnosis of GPA and evaluated the histological confirmation at diagnosis of this disease. MATERIAL AND METHODS: A retrospective analysis was performed in patients with GPA diagnosed and treated in clinics of the University Clinical Center (UCK) in Gdansk in 1988-2009. RESULTS: In the analyzed group of GPA patients the histopathological examination of biopsies taken from involved tissues (except kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%) were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were non-specific. Considering all biopsies, the diagnosis was confirmed in 24 patients (57% of patients in whom biopsies were taken). Epitheloid cell granulomas were present in 33 biopsies (43%), characteristic necrosis in 27 biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while multinucleated giant cells were identified only in 9 biopsies (12%). CONCLUSIONS: Histopathological examination of the affected tissues remains the gold standard of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative patients, in the initial phase of the disease, or in patients with atypical clinical presentation. In many cases, it is necessary to repeat biopsy to establish the diagnosis. The role of the histopathological examination seems to be particularly important when ANCA is negative or clinical symptoms are atypical of GPA.

Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis.

BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies. METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment. RESULTS: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r = 0.26 and 0.33), and so did CD68+ (r = 0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR) = 0.3, P = 0.003), CD68+ infiltration (HR = 0.2, P < 0.001), brain radiotherapy (HR = 0.1, P < 0.001), endocrine therapy (HR = 0.1, P < 0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR = 2.6, P = 0.01), HER2 expression in BCBM (HR = 4.9, P = 0.01). CONCLUSIONS: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.

Concurrent DNA Copy-Number Alterations and Mutations in Genes Related to Maintenance of Genome Stability in Uninvolved Mammary Glandular Tissue from Breast Cancer Patients.

Somatic mosaicism for DNA copy-number alterations (SMC-CNAs) is defined as gain or loss of chromosomal segments in somatic cells within a single organism. As cells harboring SMC-CNAs can undergo clonal expansion, it has been proposed that SMC-CNAs may contribute to the predisposition of these cells to genetic disease including cancer. Herein, the gross genomic alterations (>500 kbp) were characterized in uninvolved mammary glandular tissue from 59 breast cancer patients and matched samples of primary tumors and lymph node metastases. Array-based comparative genomic hybridization showed 10% (6/59) of patients harbored one to 359 large SMC-CNAs (mean: 1,328 kbp; median: 961 kbp) in a substantial portion of glandular tissue cells, distal from the primary tumor site. SMC-CNAs were partially recurrent in tumors, albeit with considerable contribution of stochastic SMC-CNAs indicating genomic destabilization. Targeted resequencing of 301 known predisposition and somatic driver loci revealed mutations and rare variants in genes related to maintenance of genomic integrity: BRCA1 (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1 (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro), and TP53 (p.Arg306*). Co-occurrence of gross SMC-CNAs along with point mutations or rare variants in genes responsible for safeguarding genomic integrity highlights the temporal and spatial neoplastic potential of uninvolved glandular tissue in breast cancer patients.

Differentiation of high-risk stage I and II colon tumors based on evaluation of CAV1 gene expression.

BACKGROUND: Several molecular markers are currently being investigated for their prognostic or predictive value in colorectal cancer. One of the genes proposed, as a potential molecular marker in CRC is CAV1. METHODS: The level of CAV1 expression was investigated in low-stage (I and II TNM) colon cancers using Real-Time PCR and immunohistochemistry. RESULTS: The level of CAV1 expression increased in tumors characterized by greater depths of invasiveness. The CAV1 expression level detected in tumors with a depth of invasion at stage T4 was significantly higher compared to that in T2 (P = 0.01) and T3 (P = 0.003) lesions. The length of a patient's survival depended on CAV1 expression level; the 10-year survival rate for patients with elevated expression of CAV1 was ∼59% compared with 91% for patients with reduced or unchanged expression of CAV1 (P = 0.007). The overall survival rate of patients with T3 + T4 lesions was significantly lower (P = 0.006) for patients with tumor displaying elevated CAV1 expression compared with patients with reduced or unchanged CAV1 expression. CONCLUSIONS: Evaluation of CAV1 expression offers valuable prognostic information for patients with colorectal cancer, and could be used to select patients with stage I or II disease, who are at increased risk of unfavorable outcomes.

Primary malignant lymphoma combined with clinically "silent" pheochromocytoma in the same adrenal gland.

An increased number of adrenal tumors are now diagnosed due to the increased number of abdominal CT scans being performed. We present the first case of malignant lymphoma combined with clinically "silent" pheochromocytoma in the same adrenal gland. An abdominal CT scan demonstrates unilateral adrenal lesion which suggests pheochromocytoma or adrenal carcinoma. Laboratory examinations revealed a slight increase of 24-h urine vanillylmandelic acid and 24-h urinary methanephrine excretion. Histological examination revealed two intermingled tumor cell proliferations-diffuse B cell lymphoma and pheochromocytoma.Unexpected coexistence of catecholamine-producing tumor with the other adrenal lesion can lead to serious complications of diagnosis and treatment. The adequate preparation for surgery can protect patient from threatening catecholamine crisis.