Background. Cutis laxa (CL) is a rare disorder of elastic tissue characterized by loose, sagging skin with reduced elasticity, and resilience without resulting scarring. CL may be inherited as a ...dominant, recessive, or X-linked recessive disease, or acquired. The heritable forms of CL predominantly begin at birth, but it may be delayed until puberty or age of 30 years with extracutaneous manifestations including pulmonary emphysema, umbilical and inguinal hernias, and gastrointestinal and vesicourinary tract diverticuli. An acquired form of the disease occurs in adults with no evidence of internal organ involvement. Objective. The aim of this case report was to present our patient suffering from CL, and to evaluate clinical presentation, diagnostic and therapeutic difficulties in this rare condition. Case Report. A 30-year-old female patient was admitted to our Hospital due to localized loose and sagging skin of abdomen, induced by prior cesarean section 6 years ago. CL has been diagnosed based on the clinical picture and pathohistological appearance. Conclusion. Reconstructive surgery provides a dramatic cosmetic improvement with significant psychosocial benefit. Repeated surgical procedures may be required to correct the lax skin, which worsens with age.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Gallbladder cancer is a rare malignancy with a very high mortality, usually due to diagnosis in an advanced stage of the disease. Therefore, the aim of this study was to evaluate the clinical ...significance of cancer/testis antigen 1A (CTAG1A, NY-ESO1) and CD274 molecule (PD-L1, the ligand for programmed cell death protein 1) and their impact on the overall survival of patients with gallbladder cancer.
Using immunohistochemical staining, we determined the expression of NY-ESO1 in tumor cells (positivity: cytoplasmic/nuclear staining of any intensity in ≥50%) and PD-L1 in tumor cells and intratumoral immune cells (positivity: cytoplasmic/membranous staining of any intensity in ≥1%).
The median overall survival (OS) of 58 patients with gallbladder cancer in our cohort was 7 months, and depended on the clinical stage of the disease; the 5-year OS rate was 10%. NY-ESO1 was expressed in 69.1% of cases. Immune cells were PD-L1-positive in 36.4% of cases, while tumor cells expressed PD-L1 in only 10.9% of cases. In six cases (10.9%), neither of the studied proteins were expressed. NY-ESO1 expression was negatively correlated with PD-L1 expression in immune cells (p=0.021). NY-ESO1 showed no correlation with any clinicopathological parameters or OS. PD-L1 expression in immune cells was significantly higher in tumors with perineural invasion (r
=0.318; p=0.018) and higher clinical disease stage (r
=0.339; p=0.013) but showed no correlation with OS.
Patients whose gallbladder cancer expresses NY-ESO1 or PD-L1 might be candidates for immunotherapy.
Key regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1, DVL2 and DVL3 were used to detect microsatellite ...instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF1 and LEF1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II (P = 0.008). Collectively, LOHs were more frequent in high‐grade tumours than in low grade ones. LOHs of DVL3 gene were significantly associated with grade IV tumours (P = 0.007). The results on protein expressions indicated that high‐grade tumours expressed less DVL1 protein as compared with low grade ones. A significant negative correlation was established between DVL1 expression and malignancy grades (P < 0.001). The expression of DVL2 protein was found similar across grades, while DVL3 expression significantly increased with malignancy grades (P < 0.001). The signal strengths of expressed DVL1 and DVL3 were negatively correlated (P = 0.002). However, TCF1 and LEF1 were both significantly upregulated and increasing with astrocytoma grades (P = 0.001). A positive correlation was established between DVL3 and both TCF1 (P = 0.020) and LEF1 (P = 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that DVL1 and DVL2 may be involved during early stages of the disease, while DVL3 may have a role in later phases and together with TCF1 and LEF1 promotes the activation of Wnt signalling.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Neuroendocrine breast cancer (NEBC) is a group of rare tumors, which could benefit from therapy targeting the somatostatin receptors (SSTRs). In particular, SSTR2A and SSTR5 are potential targets ...given their consistent expression in gastrointestinal and pancreatic primary and metastatic neuroendocrine cancers. Currently, there are no studies describing the expression of SSTRs in NEBC. The purpose of our study was to characterize the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of NEBC.
Thirty-one primary NEBC cases were analyzed, and SSTR2A and SSTR5 immunohistochemistry performed and scored using the modified immunoreactive score proposed by Remmele and Stanger.
All patients were females with a mean age of 66.6 years (SD = 14). 77% of cases were histological grade 2. SSTR2A showed a weak positivity in 11 cases (35.5%), moderate positivity in 6 cases (19.4%) and strong positivity in 5 cases (16.1%). Nine cases were negative for SSTR2A (29%). SSTR5 showed a weak positivity in 16 cases (51.6%), moderate positivity in 6 cases (19.4%), while no cases showed strong positivity. Nine cases were negative for SSTR5 (29%). Five cases were negative for both SSTR2A and SSTR5.
A weak to moderate SSTR2A and SSTR5 expression was observed in 50–70% of the cases. A subset of NEBCs with strong SSR2A expression may benefit from SSTRs targeted therapy. These results need further validation in a larger series including metastatic NEBC, to provide potential therapeutic targets for patients with advanced disease.
•We analyzed the immunohistochemical expression of SSTR2A and SSTR5 in women with neuroendocrine breast cancer.•We show expression of SSTR2A and SSTR5 in the majority of analyzed cases.•SSTR2A and SSTR5 could be potential therapeutic targets for localized and advanced neuroendocrine breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this study, the level and distribution of transferrin receptor 1 (TfR1) and ferritin in colorectal carcinoma and in normal colon epithelium has been determined relative to the tumor stage and iron ...status of patients using immunohistochemical staining methods. While the majority of carcinoma patients were anemic, no relationship between the level of colon tissue ferritin and TfR1 and the systemic parameters of iron metabolism was evident. Furthermore, no association between ferritin content and the grade of colorectal carcinoma was observed. However, a relationship between the expression of TfR1 and the grade of colorectal carcinoma was observed. In this case high expression of TfR1 was found in colorectal carcinoma samples of Dukes A or B grade, and well differentiated colorectal carcinoma cells. In comparison, weak or no expression of TfR1 was observed in carcinoma samples of Dukes C or D grade with poorly differentiated cells and in carcinoma samples that had lymph node infiltration and distant metastasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We describe a rare case of an eccrine syringofibroadenoma with a foci of squamous cell carcinoma in situ, which has to best of our knowledge been reported only twice in the English literature. An ...excisional biopsy of an elevated, lobular tumor of the lower leg in an 86-year-old male patient was performed. Histologic examination revealed a tumor consisting of anastomosing strands of epithelial cells originating from the epidermis, occasionally showing ductal eccrine differentiation. Foci of squamous cell carcinoma in situ were observed within the described lesion. The diagnosis of eccrine syringofibroadenoma with squamous cell carcinoma in situ was established. Eccrine syringofibroadenoma is a rare lesion, mostly considered to be a reactive process arising secondarily in association with other cutaneous diseases such as dermatoses or neoplasms, although some researchers do not exclude the possibility that it is a primary neoplasm with a potential for malignant transformation.
Ghrelin is an adipokine that plays an important role in energy balance. Expression of ghrelin and ghrelin receptor has been investigated in different tissues and tumors. Studies regarding expression ...of ghrelin and ghrelin receptor in colorectal tumors are scarce and no data on expression of ghrelin and its receptor in colorectal adenomas has been published. Ghrelin and ghrelin receptor were highly expressed in colon carcinoma cells while expression was decreased in less differentiated tumors, presuming that ghrelin might be important in early phases of tumorigenesis.
To investigate the expression of ghrelin and ghrelin receptor in human colorectal adenomas and adjacent colorectal tissue.
In this prospective study (conducted from June 2015 until May 2019) we included 92 patients (64 male and 28 female) who underwent polypectomy for colorectal adenomas in the Department of Gastroenterology and Hepatology, "Sestre milosrdnice" Clinical Hospital Center in Zagreb, Croatia. After endoscopic removal of colorectal adenoma, an additional sample of colon mucosa in the proximity of the adenoma was collected for pathohistological analysis. Adenomas were graded according to the stage of dysplasia, and ghrelin and ghrelin receptor expression were determined immunohistochemically in both adenoma and adjacent colon tissue using the polyclonal antibody for ghrelin (ab150514, ABCAM Inc, Cambridge, United States) and ghrelin receptor (ab48285, ABCAM Inc, Cambridge, United States). Categorical and nominal variables were described through frequencies and proportions and the difference between specific groups were analyzed with Fisher's and Fisher-Freeman-Halton's method respectively. Spearman's rank correlation coefficient was determined for correlation of expression of ghrelin and ghrelin receptor in adenoma and adjacent colon tissue with the grade of adenoma dysplasia.
Among 92 patients with colorectal adenoma 43 had adenomas with high-grade dysplasia (46.7%). High expression of ghrelin was 7 times more common in high-grade adenoma compared to low-grade adenomas (13.95% to 2.04%,
= 0.048), while the expression of ghrelin in adjacent colon tissue was low. We found no correlation between ghrelin receptor expression in adenoma and adjacent colon tissue and the grade of colorectal adenoma dysplasia. The most significant correlation was found between ghrelin and ghrelin receptor expression in adenomas with high-grade dysplasia (rho = 0.519,
< 0.001).
Ghrelin and ghrelin receptor are expressed in colorectal adenoma and adjacent tissue with ghrelin expression being more pronounced in high grade dysplasia as a possible consequence of increased local synthesis.
Abstract
Key regulators of the Wnt signalling,
DVL
1,
DVL
2 and
DVL
3, in astrocytomas of different malignancy grades were investigated. Markers for
DVL
1
,
DVL
2
and
DVL
3
were used to detect ...microsatellite instability (
MSI
) and gross deletions (
LOH
), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three
DVL
proteins and transcription factors of the pathway,
TCF
1 and
LEF
1. Our findings demonstrated that
MSI
at all three
DVL
loci was constantly found across tumour grades with the highest number in grade
II
(
P
= 0.008). Collectively,
LOH
s were more frequent in high‐grade tumours than in low grade ones.
LOH
s of
DVL
3
gene were significantly associated with grade
IV
tumours (
P
= 0.007). The results on protein expressions indicated that high‐grade tumours expressed less
DVL
1 protein as compared with low grade ones. A significant negative correlation was established between
DVL
1 expression and malignancy grades (
P
< 0.001). The expression of
DVL
2 protein was found similar across grades, while
DVL
3 expression significantly increased with malignancy grades (
P
< 0.001). The signal strengths of expressed
DVL
1 and
DVL
3 were negatively correlated (
P
= 0.002). However,
TCF
1 and
LEF
1 were both significantly upregulated and increasing with astrocytoma grades (
P
= 0.001). A positive correlation was established between
DVL
3 and both
TCF
1 (
P
= 0.020) and
LEF
1 (
P
= 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that
DVL
1 and
DVL
2 may be involved during early stages of the disease, while
DVL
3 may have a role in later phases and together with
TCF
1 and
LEF
1 promotes the activation of Wnt signalling.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To determine the predictive value of HIF-1α and VEGF-C in primary neuroendocrine breast cancers (NEBC) and their correlation with other clinico-pathological characteristics of NEBC.
HIF-1α and VEGF-C ...were determined immunohistochemically in tissue samples from 31 cases of NEBC.
The HIF-1α expression in NEBC was predominantly negative, with only 5 (16.1%) cases showing strong reaction to HIF-1α. Eighteen (58.0%) NEBC cases showed moderate-to-strong VEGF-C expression. VEGF-C expression negatively correlated with progesterone receptor positivity (p=0.014) and duration of follow-up (p=0.021). A multivariate Cox proportional hazard regression analysis showed that HIF-1α (p=0.019) was a significant predictor of disease-free survival, whereas VEGF-C (p=0.099) showed no such association.
HIF-1α overexpression indicated unfavourable prognosis and could serve as an additional prognostic factor in NEBC. Moreover, patients with NEBC exhibiting moderate or strong VEGF-C expression could be candidates for a specific VEGF-C antibody therapy.
Apoptosis plays an important role in regulating skin development and homeostasis, as well as carcinogenesis. Apoptosis balances epidermal proliferation to maintain epidermal thickness and may ...eliminate mutated, premalignant cells. Skin carcinomas are the most common cancers in Western population. The risk is closely related to UV exposure and the relation between exposure to UV radiation and development of skin cancer has been well established. Apoptosis and carcinogenesis in skin can be triggered by UV irradiation, and tumor suppressor gene p53 plays the most important role in these two processes. The p53 gene is involved in the cell cycle arrest and activation of apoptosis. It has been shown that p53 could protect skin cells from DNA-damage due to UVB exposure. UV-induced DNA damage activates the mechanisms for removal of DNA damage, delay in cell cycle progression, DNA repair, or apoptosis by transcriptional activation of p-53 related genes, such as p21 and bax. Several studies have shown that UVB also induces mutations in p53 gene.The induced mutations are unique (C toT and CC to TT transition) for UVB radiation and are not commonly induced by other carcinogens. Mutations in the p53 gene have been detected in 50% of all human cancers and in the majority of skin carcinomas. A high frequency of p53 mutation was reported in pre-malignant actinic keratosis lesions that is considered to be pre-squamous cell carcinoma, and in Bowen's disease that is considered to be in situ squamous cell carcinoma (SCC) of the skin. The majority of these mutations were characteristic UVB mutations and these findings suggested that p53 mutations might be involved in the malignant conversion of precancerous lesions to SCC. Several studies have demonstrated the continued and discontinued regimens of chronic UVB treatment to ultimately result in skin tumor development with 100% incidence, although the kinetics of tumor occurrence is delayed in the latter. Thus, these studies suggest that skin cancer development can be delayed but not stopped with further avoidance of UV exposure. More recent studies have shown that besides UVB, UVA component of solar irradiation could also be an important carcinogen but in the stem cell compartment of the skin. This knowledge will lead to development of new apoptosis-based therapeutics; several have recently been tested in SCC. It can be expected that new apoptosis-based drugs are to be introduced soon to the daily medical practice; however, prevention of excessive UVB exposure remains the main curative factor against skin cancer.
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