Should we use risk selection tests for HPV 16 and/or 18 positive cases: Comparison of p16/Ki67 and cytology.

Major screening abnormalities in precolposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary human papillomavirus (HPV)-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Among 30 066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available high-risk types of HPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher positive predictive value for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p < 0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2.26/2.19 vs. 3.54). Only one HSIL+ case was missed in both triage models with DS incorporation. p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

HPV related p16INK4A and HSV in benign and potentially malignant oral mucosa pathologies.

BACKGROUND: The association of Human Papilloma Virus (HPV) and Human Syncytial Virus (HSV) infection with inflammatory and potentially malignant disorders of the oral cavity (OPMD) is unknown. The aim of this cross-sectional study was to stablish the expression of the p16INK4A and HSV proteins, to test potential correlation between those parameters in biopsies from clinically diagnosed oral lesions. METHODS: Immunochemical analysis of 211 formalin-fixed, paraffin-embedded (FFPE) blocks from 211 individuals was provided. The clinical diagnosis included in the research were Oral lichen planus (N = 30), Oral Leukoplakia (N = 13) Mucocele (N = 25), Erosion/ulceration/ inflammation of mucosa (N = 8), Overgrowth of mucosa (N = 135). RESULTS: Two hundred eleven analyzed FFPE samples resulted with the median age of 58.5 years (the average age 54.0 years and SD ± 17 years). The female/male ratio was 2.3 (69.7% vs 30.3% respectively). All the samples positive for HSV also expressed p16INK4A (p = 0.000), that's showed various levels of association with the diverse clinical diagnosis reaching the higher level in OM 49.1% (29 positive samples) and OLP 30.5% (18). p16INK4A was associated with OLP at 30.5% (18), and fibroma 30.5%. HSV expression was mostly present in fibroma at 47.6% (10 positive samples). CONCLUSION: HSV and p16INK4A positivity in relation to diagnosis of the biopsies showed statistically most often p16INK4A in OLP and fibroma. The results of co-expression of p16INK4A and HSV in mucocele and fibroma in oral mucosa suggest a cooperation between the molecular alterations induced by these two viruses. Squamous papilloma samples positive for p16INK4A were also positive for HSV, suggesting that the putative pro-oncogenic action of HSV could be an early event.

p16/Ki67 dual stain triage versus cytology in primary human papillomavirus-based cervical cancer screening with limited genotyping.

The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2-55.8; p < 0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention.

Histology of Liver of the Deceased Due to Harmful Use of Alcohol.

AIM: To study types and incidence of histological changes in liver of people deceased due to harmful use of alcohol. METHODS: A retrospective review of medico-legal autopsy of 236 adults who died in the years 2015-2016 due to harmful use of alcohol was done. Histopathological liver samples taken during autopsies were evaluated. Blood alcohol content was analyzed. Serological tests for hepatitis B surface antigen and anti-hepatitis C virus (HCV) were performed. RESULTS: The most common liver pathology (83.1%) was steatosis, mainly mixed type (50%); 66.9% had high-grade steatosis. Liver fibrosis was detected in 39.4% of cases, with fibrosis of higher than or equal to third grade in 14%, hepatitis in 44.5% and steatohepatitis in 19.1%. Toxic hepatocyte injury features (ballooning degeneration, Mallory-Denk bodies) were found in 20.8% cases and degenerative-damage changes in 41.1%. The correlation between the grade of steatosis and fibrosis (P = 0.0005), toxic injury (0.00000101) and degenerative-traumatic changes (P = 0.00000741) was found. The correlation was found between hepatitis and higher than or equal to third grade steatosis (P = 0.037), cholestasis (P = 0.0139), toxic injury features (P = 2.58 × 10-13), degenerative-damage changes (P = 7.9 × 10-12) and presence of anti-HCV (P = 0.00723) and between progression of fibrosis and presence of toxic injury features (2.28 × 10-19), degenerative-damage changes (P = 4.25 × 10-11) and anti-HCV (P = 0.0263). CONCLUSIONS: Spectrum of histopathological liver changes is broad regardless of sex, and various traits are present in various patterns. Comorbidities have strong influence on the picture of changes in the liver. Exact evaluation how often and what histopathological changes will develop in alcohol liver disease is not possible by reason of variability of external factors.

Prevalence and clinical presentation of lymphoproliferative disorder in patients with primary Sjögren's syndrome.

Lymphomas are one of the serious complications of the primary Sjörgen's Syndrome (pSS). The aim of the study was to evaluate the frequency of lymphoma in pSS. The singe-center retrospective study included 198 Caucasian patients, who met diagnostic criteria for pSS. The type of lymphoproliferative disorder was classified according to the WHO 2016 classification. The mean time of observation, after pSS diagnosis, was 48 weeks. Focus score (FS) ≥ 1 was present in 85% of the patients, and anti-SSA antibodies were detected in 84%. Rheumatoid factor was detected in 130 (65%) patients. Mean disease activity index, according to EULAR Sjörgen's Syndrome disease activity index (ESSDAI), was 8.3 points at the moment of pSS diagnosis. Complement C3 was decreased in 14% of the patients, while 10% showed reduced complement C4. Four patients (2%) were diagnosed with a lymphoma. Most of the patients were diagnosed with mucosa-associated lymphoid tissue lymphoma (MALT), in whom the tumour was located in the parotid gland, and in one patient the stomach was involved. Finally, one patient was diagnosed with a rare B-cell small lymphocytic lymphoma located in the lungs. In this article, we present detailed characteristics of each case. In analysed population the frequency of lymphoma in the course of pSS in patients with pSS is 2%. The variety of lymphoma types in pSS patients imposes individual monitoring in each patient at every check-up visit for disease activity.

Filler Migration and Florid Granulomatous Reaction to Hyaluronic Acid Mimicking a Buccal Tumor.

Hyaluronic acid is among the most commonly used cosmetic fillers. Although considered biocompatible and safe, it may rarely cause a wide range of complications. The authors report a case of migration of hyaluronic acid concomitant with granulomatous inflammatory response that mimicked a buccal tumor. A 52-year-old female presented with a solid painless mass of the right buccal area. The patient denied any history of trauma and cosmetic procedures of the affected area. Skin and mucosal membrane were intact and the lesion was firm and well fixed in the deep plane. Due to worrisome clinical presentation and the patient's history of breast cancer, the lesion was excised radically. Histopathological examination revealed multiple granulomas surrounding amorphous lakes of hyaluronic acid. During repeated, thorough anamnesis the patient admitted having underwent lip augmentation and nasolabial fold correction with HA two years before, after which the filler must have migrated posteriorly. Physicians need to be aware of various complications associated with cosmetic fillers as they may mimic severe clinical conditions.

Histopathological assessment of oral leukoplakia. Osteonectin as possible biomarker for further diagnostics.

Clinical evaluation of oral leukoplakia (OL), confirmed by the histological evaluation of the suspected area, provides the gold standard for diagnostics of this pathology. The aim of present study was to encrypt the significance of the histopathological results (oral intraepithelial neoplasia - OIN, WHO 2005, Ljubljana classification systems) of OL. The usefulness of osteonectin as a biomarker of changes in the oral cavity epithelium was evaluated. IRS Score to evaluate osteonectin (SPARC - secreted protein acidic and rich in cysteine) production in oral mucous tissues was modified, with the aim of adapting the diagnostic measurements to the OL cell environment. In total, 37 formalin-fixed, paraffin-embedded (FFPE) blocks from patients with clinically diagnosed OL, and 29 FFPE blocks from patients with OSCC were evaluated. The OIN and system from Ljubljana were compared, to adjudicate which was most compatible with WHO 2005 histopathological assessment. Increased production of SPARC was observed, with the progression in severity of pathological changes in the oral mucosa, from simple hyperplasia, through dysplasia, to OSCC. The WHO 2005 and the OIN classification systems can be applied interchangeably.

Immunohistochemical and ultrastructural analysis of sporadic inclusion body myositis: a case series.

Sporadic inclusion body myositis (s-IBM) is a progressive, skeletal muscle disease with poor prognosis. However, establishing the final diagnosis is difficult because of the lack of clear biomarkers in the blood serum and very slow development of clinical symptoms. Moreover, most other organs function normally without any disturbance. Here, in patients with this untreatable disease, we have underlined the importance of immunohistochemical and ultrastructural assessment of skeletal muscle in patients diagnosed with s-IBM. The goal of this study was to identify the distribution of specific antigens and to determine morphological features in order to localize pathological protein aggregates, rimmed vacuoles, and loss of myofibrils, which are key elements in the diagnosis of s-IBM. All studied patients were between 48 and 83 years of age and were hospitalized in the Department of Rheumatology and Internal Medicine between 2011 and 2016. Anamneses revealed an accelerated progression of muscle atrophy, weakness of limb muscles, and difficulties with climbing stairs. Based on histopathology and transmission electron microscopy examination, inflammatory infiltrations consisting of mononuclear cells, severe atrophy and focal necrosis of myofibers, splitting of myofilaments, myelinoid bodies and rimmed vacuoles were observed. Primary antibodies directed against CD3, CD8, CD68, cN1A, beta-amyloid, Tau protein and apolipoprotein B made it possible to identify types of cells within infiltrations as well as the protein deposits within myofibers. Using a combination of immunohistochemistry and electron microscopy methods, we were able to establish the correct final diagnosis and to implement a specific treatment to inhibit disease progression.

Nuclear pseudoinclusions in melanoma cells: prognostic fact or artifact? The possible role of Golgi phosphoprotein 3 overexpression in nuclear pseudoinclusions generation.

Nuclear pseudoinclusions (NPIs) are classically found in papillary thyroid carcinoma and meningioma. Although NPIs have been described in melanocytic lesions, there is no systematic analysis of potential relationship between NPIs and other clinicopathological characteristics of melanoma. We examined the presence of NPIs in H&E-stained tissue sections form 96 melanomas and analyzed statistical associations with important clinicopathological parameters and tissue immunoreactivity for selected proteins involved in epithelial-mesenchymal transition (SPARC, N-cadherin), cell adhesion and mobility (ALCAM, ADAM-10), regulation of mitosis (PLK1), cell survival (FOXP1) and functioning of Golgi apparatus (GOLPH3, GP73). NPIs were observed in 20% of melanomas and their presence correlated with high mitotic rate and ulceration of the tumor, but not with Breslow thickness, histologic type, or presence of metastases. We observed a significant correlation with shorter cancer-specific survival, but not disease-free survival. Presence of NPIs was related to high expression of GOLPH3 in melanoma cells, whereas their absence was linked to enhanced immunoreactivity of GOLPH3 in tumor-associated macrophages. NPIs are not an uncommon finding in skin melanoma and their diagnostic and prognostic utility could be helpful in the daily routine histopathological practice. The possible explanation of NPI generation is associated with enhanced activity of Golgi apparatus in melanoma cells.

Diagnostic Difficulties in Primary Pauci-Melanotic Leptomeningeal Melanomatosis.

We present a rare case of primary malignant melanoma of the central nervous system. We underline the difficulties we faced during diagnostic procedures. Finally, postmortem examination revealed the diagnosis of primary pauci--melanotic leptomeningeal melanomatosis.

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.

Biological Aggressiveness of Subclinical No-Mass Ductal Carcinoma In Situ (DCIS) Can Be Reflected by the Expression Profiles of Epithelial-Mesenchymal Transition Triggers.

Epithelial-mesenchymal transitions (EMTs) have been recently implicated in the process of cancer progression. The aim of this study was to assess how the preoperative expression patterns of EMT biomarkers correlate with the risk of postoperative invasion in ductal carcinoma in situ (DCIS) found on stereotactic breast biopsies. N-cadherin, Snail1, and secreted protein acidic and rich in cysteine (SPARC) immunoreactivity was observed in 8%, 62%, and 38% of tumors, respectively. Snail1 and SPARC expressions were significantly related to N-cadherin expression and to each other. The postoperative upgrading rate was associated with a positive preoperative expression of all biomarkers. Significance of Snail1 and SPARC persisted in multivariate analysis, but the impact of SPARC on invasion was more significant. When these two EMT triggers were considered together, the risk of invasion did not significantly differ between the subtypes of DCIS with single positive expression (SPARC-/Snail1+ vs. SPARC+/Snail1-). However, it was significantly lower in single-positive DCIS when compared to lesions of a double-positive profile (SPARC+/Snail1+). Moreover, there were no cases in the double-negative DCIS (SPARC-/Snail1-), with foci of infiltrating cancer found postoperatively in residual postbiopsy lesions. In contrast, DCIS with a combined high SPARC and Snail1 expression (intermediate or strong) had an invasive component in 66⁻100% of tumors.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

Epithelial-mesenchymal transition inducer Snail1 and invasive potential of intraductal breast cancer.

BACKGROUND AND OBJECTIVES: Transcription factor Snail1 is a key inducer of epithelial-mesenchymal transition (EMT), a biological process implicated in the cancer progression and metastasis. The aim of the study was to investigate Snail1 expression in DCIS found on breast biopsy and assess its predictive value for the final invasion. METHODS: A total of 209 patients with histologically diagnosed pure DCIS entered the study. Snail1 reactivity was evaluated with immunohistochemistry in tumor tissue from stereotactic vacuum-assisted biopsy of suspicious microcalcifications. RESULTS: Snail1 staining was observed in 62% of tumors: weak, intermediate, and strong in 27%, 21%, and 14% of lesions, respectively. Positive Snail1 expression was significantly rarer in DCIS presenting as powdery microcalcifications, when compared with crushed stone-like and casting-type and was more common in DCIS with comedonecrosis. Correlation with other features was not significant. None of standard parameters significantly influenced the upgrading rate. In contrast, in uni- and multivariate analysis the risk of postoperative invasion was significantly associated with positive Snail1 immunoreactivity. Moreover, there was a significant stepwise increase of upgrading rate according to Snail1 expression in DCIS cells: weak 9%, intermediate 26%, and strong 55%, respectively. CONCLUSIONS: Snail1 can reflect the invasive potential of DCIS and help identify its more aggressive subtypes.

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.

Role of vascular endothelial growth factor in inducing production of angiopoetin-1 - in vivo study in Fisher rats.

The aim of the study was to investigate how an intramuscular injection of plasmids with genes coding various pro-angiogenic factors: angiopoetin-1 (ANGPT1), vascular endothelial growth factor (VEGF165) and hepatic growth factor (HGF), influences the production of ANGPT1. 40 Healthy Fisher rats received i.m. injections containing plasmids encoding pro-angiogenic genes in thigh muscles. They were divided into four equal groups. The first group received the plANGPT1 plasmid and the second group- the pIRES/ANGPT1/VEGF165 bicistronic plasmid. The pIRES/VEGF165/HGF bicistronic plasmid was administered to the third group and an empty plasmid (control group) to the fourth group. The animals were euthanized after 12 weeks. In each group, the number of vessels stained with the anti-ANGPT1 antibody was assessed under an optical microscope. The anti-ANGPT1 antibodies stained the vessels in all the groups. There were on average 14.1 ±2.3 vessels in the the plANGPT1 group, 32.5 ±10.5 in the pl/RESANGPT1/VEGF group and 30.8 ±13.3 in the plRES/HGV/VEGF group. There were on average 7.3 ±2.3 stained vessels (p < 0.0001) in the control group . The VEGF plays a role in the induction of the production of ANGPT1. The administration of plasmids only encoding ANGPT1 does not induce its production.

A review on Eph/ephrin, angiogenesis and lymphangiogenesis in gastric, colorectal and pancreatic cancers.

Erythroprotein-producing human hepatocellular carcinoma receptors (Eph receptors) compose a subfamily of transmembrane protein-tyrosine kinases receptors that takes part in numerous physiological and pathological processes. Eph family receptor-interacting proteins (Ephrins) are ligands for those receptors. Eph/ephrin system is responsible for the cytoskeleton activity, cell adhesion, intercellular connection, cellular shape as well as cell motility. It affects neuron development and functioning, bone and glucose homeostasis, immune system and correct function of enterocytes. Moreover Eph/ephrin system is one of the crucial ones in angiogenesis and lymphangiogenesis. With such a wide range of impact it is clear that disturbed function of this system leads to pathology. Eph/ephrin system is involved in carcinogenesis and cancer progression. Although the idea of participation of ephrin in carcinogenesis is obvious, the exact way remains unclear because of complex bi-directional signaling and cross-talks with other pathways. Further studies are necessary to find a new target for treatment.

Ductal carcinoma in situ on stereotactic biopsy of suspicious breast microcalcifications: Expression of SPARC (Secreted Protein, Acidic and Rich in Cysteine) can predict postoperative invasion.

BACKGROUND AND OBJECTIVES: Secreted protein, acidic and rich in cysteine (SPARC) is able to play an important role in cancer invasion due to de-adhesive properties and impact on stromal remodeling. The aim of study was to investigate SPARC expression in preoperatively diagnosed breast DCIS and to assess its predictive value for the final invasion. METHODS: A total of 209 patients with DCIS found on stereotactic vacuum-assisted biopsy of suspicious microcalcifications were studied prospectively. RESULTS: SPARC staining was positive in luminal epithelial cells, stromal fibroblasts, and myoepithelial cells in 38%, 62%, and 61% of tumors, respectively. Neither patient age nor pattern of microcalcifications were related to SPARC expression. High nuclear grade and comedonecrosis were associated with strong immunoreactivity of SPARC in stromal fibroblasts and myoepithelial cells while not in luminal epithelial cells. Rate of postoperative invasion was significantly increased in DCIS with strong SPARC staining with regard to all investigated cells. None of standard parameters significantly influenced the upgrading risk. In multivariate analysis most significant and independent predictive factors were strong SPARC expression in luminal epithelial cells, and stromal fibroblasts. CONCLUSIONS: SPARC can be a new biomarker helpful to identify more aggressive DCIS and for prediction of invasive disease on final pathology. J. Surg. Oncol. 2016;114:548-556. © 2016 Wiley Periodicals, Inc.

Golgi-Related Proteins GOLPH2 (GP73/GOLM1) and GOLPH3 (GOPP1/MIDAS) in Cutaneous Melanoma: Patterns of Expression and Prognostic Significance.

GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS). On the contrary, increased numbers of GOLPH2-positive and GOLPH3-positive TAMs were observed in thinner, non-ulcerated tumors, with brisk lymphocytic reaction and absent lymphangioinvasion. Distant metastases were not observed among patients with high numbers of GOLPH2-positive TAMs. Increased expression of either protein in TAMs was related to prolonged CSOS and DFS. Similarly, GOLPH3-expressing CAFs were more frequent in thin melanomas with low mitotic rate, without ulceration and lymphangioinvasion. Moreover, increased GOLPH3-positive CAFs correlated with the absence of regional or distant metastases, and with longer CSOS and DFS. GOLPH2 expression was not observed in CAFs. Our results suggest that GOLPH2 and GOLPH3 play a role in melanoma progression and are potential targets for molecular-based therapies.

Screen-detected ductal carcinoma in situ found on stereotactic vacuum-assisted biopsy of suspicious microcalcifications without mass: radiological-histological correlation.

BACKGROUND: Commonly identified on screening mammography breast microcalcifications are the predominant manifestation of ductal carcinoma in situ (DCIS). The aim of this study was to investigate the association between clinico-radiological features and histological findings in patients with screen-detected DCIS. PATIENTS AND METHODS: Consecutive 127 patients with pure DCIS found on stereotactic vacuum-assisted biopsy of screen-detected suspicious microcalcifications without mass entered the study. Patient age, type and distribution of microcalcifications, DCIS nuclear grade (NG) and the presence of comedonecrosis were investigated. Association between parameters was statistically analysed with P < 0.05 as a significance level. Results. Powdery microcalcifications were most often clustered while regional were most common of casting-type (P < 0.001). High, intermediate and low NG of DCIS was significantly related to casting-type, crushed stone-like and powdery microcalcifications, respectively (P < 0.01). Low and intermediate NG DCIS were the most common in clustered and grouped microcalcifications while high NG DCIS was the most often when regional distribution was observed (P < 0.05). Comedonecrosis was significantly more common in high NG DCIS (P < 0.01). The association between comedonecrosis and type of microcalcifications was not significant, but with their distribution was close to the significance level (P = 0.07). Patient age was not significantly related to imaging or histological findings. CONCLUSIONS: The association between pattern of mammographic microcalcifications and histological findings related to more aggressive disease can be helpful in optimal surgery planning in patients with screen-detected DCIS, regarding the extent of breast intervention and consideration of synchronous sentinel node biopsy.