The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06−0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12–0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.

Although aldo-keto reductases (AKRs) have been widely studied in cancer, no study to date has examined the roles of AKR family 1 members B1 (AKR1B1) and B10 (AKR1B10) in a large group of ovarian cancer patients. AKR1B1 and AKR1B10 play a significant role in inflammation and the metabolism of different chemotherapeutics as well as cell differentiation, proliferation, and apoptosis. Due to these functions, we examined the potential of AKR1B1 and AKR1B10 as tissue biomarkers. We assessed the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 99 patients with high-grade serous ovarian cancer (HGSC) and compared these levels with clinicopathological characteristics, survival, and response to chemotherapy. A higher immunohistochemical AKR1B1 expression correlated with a better overall and disease-free survival of HGSC patients whereas AKR1B10 expression did not show any significant differences. A multivariant Cox analysis demonstrated that a high AKR1B1 expression was an important prognostic factor for both overall and disease-free survival. However, AKR1B1 and AKR1B10 were not associated with different responses to chemotherapy. Our data suggest that AKR1B1 is involved in the pathogenesis of HGSC and is a potential prognostic biomarker for this cancer.

The roles of aldo-keto reductase family 1 member B1 (AKR1B1) and B10 (AKR1B10) in the pathogenesis of many cancers have been widely reported but only briefly studied in endometrial cancer. To clarify the potential of AKR1B1 and AKR1B10 as tissue biomarkers of endometrial cancer, we evaluated the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 101 well-characterized patients with endometrioid endometrial cancer and 12 patients with serous endometrial cancer and compared them with the clinicopathological data. Significantly higher immunohistochemical levels of AKR1B1 and AKR1B10 were found in adjacent non-neoplastic endometrial tissue compared to endometrioid endometrial cancer. A trend for better survival was observed in patients with higher immunohistochemical AKR1B1 and AKR1B10 levels. However, no statistically significant differences in overall survival or disease-free survival were observed when AKR1B1 or AKR1B10 were examined individually in endometrioid endometrial cancer. However, analysis of AKR1B1 and AKR1B10 together revealed significantly better overall and disease-free survival in patients with both AKR1B1 and AKR1B10 staining above the median values compared to all other patients. Multivariant Cox analysis identified strong AKR1B1 and AKR1B10 staining as a statistically important survival prediction factor. Conversely, no significant differences were found in serous endometrial cancer. Our results suggest that AKR1B1 and AKR1B10 play protective roles in endometrioid endometrial cancer and show potential as prognostic biomarkers.

Estrogens have important roles in endometrial cancer (EC) and exert biological effects through the classical estrogen receptors (ERs) ERα and ERβ, and the G-protein–coupled ER, GPER. So far, the co-expression of these three types of ERs has not been studied in EC. We investigated ERα, ERβ, GPER mRNA and protein levels, and their intracellular protein distributions in EC tissue and in adjacent control endometrial tissue. Compared to control endometrial tissue, immunoreactivity for ERα in EC tissue was weaker for nuclei with minor, but unchanged, cytoplasmic staining; mRNA and protein levels showed decreased patterns for ERα in EC tissue. For ERβ, across both tissue types, the immunoreactivity was unchanged for nuclei and cytoplasm, although EC tissues again showed lower mRNA and protein levels compared to adjacent control endometrial tissue. The immunoreactivity of GPER as well as mRNA levels of GPER were unchanged across cancer and control endometrial tissues, while protein levels were lower in EC tissue. Statistically significant correlations of estrogen receptor α (ESR1) versus estrogen receptor β (ESR2) and GPER variant 3,4 versus ESR1 and ESR2 was seen at the mRNA level. At the protein level studied with Western blotting, there was significant correlation of ERα versus GPER, and ERβ versus GPER. While in clinical practice the expression of ERα is routinely tested in EC tissue, ERβ and GPER need to be further studied to examine their potential as prognostic markers, provided that specific and validated antibodies are available.

Subchondroplasty is a new minimally invasive surgical technique developed to treat bone marrow lesions (BML) and early osteoarthritis (OA). During the procedure, engineered calcium phosphate compound (CPC) is injected. It is claimed by the manufacturer that during the healing process, the CPC is replaced with new bone. The purpose of this study was to verify the replacement of CPC with new bone after subchondroplasty for the first time in humans. A 76-year old woman was referred for resistant medial knee pain. Standing radiographs showed varus knee OA and magnetic resonance imaging (MRI) revealed BML. She was treated with subchondroplasty of medial femoral condyle. Excellent relief of pain was achieved after procedure. Afterwards, the pain worsened, the radiographs confirmed the OA progression and the patient was treated with a total knee arthroplasty (TKA) 4 years after primary procedure. The resected bone was examined histologically and with micro-computed tomography (CT). Histologically, bone trabeculae of subcortical bone were embedded in the amorphous mass. However, no signs of CPC resorption and/or bone replacement have been found with micro-CT. In short term, excellent pain relief could be expected after the subchondroplasty procedure. However, there was no replacement of CPC with bone and the technique probably did not influence the natural process of knee OA.

Cytomegalovirus (CMV) is a common cause of infection in immunocompromised individuals, such as patients with hematological malignancies or AIDS, but can also occur in patients with other acquired immunodeficiencies. In tissue-invasive diseases, CMV diagnosis requires CMV DNA in the plasma and the histological confirmation of CMV in a tissue or organ. Evidence of CMV colitis requires a characteristic endoscopic picture with ulcers with a well-defined, convex appearance and CMV viral inclusions in the form of an “owl’s eye” on mucosal sections stained with hematoxylin and eosin. CMV-specific immunohistochemistry is the gold standard for identifying CMV in tissue biopsies. It is important to consider a CMV infection in the diagnostic process, as it may delay the diagnosis and the treatment. We present the case of a 78-year-old patient with amiodarone interstitial lung disease who was treated with methylprednisolone. Two weeks after the start of his treatment, he was admitted to the hospital for acute gastroenterocolitis and Addisonian crisis. An examination had confirmed a tissue-invasive CMV disease. He was treated with valganciclovir for a total of six weeks. After the completion of treatment, the patient showed no clinical signs of CMV infection, and both laboratory and histological examinations revealed no residual CMV disease. Tissue-invasive CMV disease can occur in patients with acquired immunodeficiency, which may result from various causes, including glucocorticoid treatment.