Unusual finding of endocervical-like mucinous epithelium in continuity with urothelium in endocervicosis of the urinary bladder

Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urothelium's expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion

Loss of PTEN expression is associated with IGFBP2 expression, younger age, and late stage in triple-negative breast cancer

© American Society for Clinical Pathology. Objectives: To investigate the association between PTEN loss and IGFBP2 expression in a series of triple-negative breast cancers and to relate this expression to basal cytokeratin expression and clinicopathologic features. Methods: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining. Results: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation ( P = .026), cytokeratin 5/6 positivity ( P = .028), and IGFBP2 expression ( P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity ( P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant. Conclusions: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression

Relationships between fish stock changes in the Baltic Sea and the M74 syndrome, a reproductive disorder of Atlantic salmon (Salmo salar)

The M74 syndrome of Baltic salmon (Salmo salar), which appears as increased yolk-sac fry mortality (YSFM), impairs the reproduction of salmon stocks. Changes in the prey stocks of Baltic salmon in its two feeding areas, the southern Baltic Proper (BPr), where sprat (Sprattus sprattus) was the main prey species during the high incidence of M74, and the Bothnian Sea, where herring (Clupea harengus) is the dominant species, were analysed in relation to salmon growth and size and in relation to the incidence of M74. The high condition factor (CF . 1.05) of prespawning salmon predicted high YSFM. From the various stock factors of sprat and herring in the southern BPr, the biomass of sprat had the strongest positive relationships with the CF of prespawning salmon, and the total prey biomass with YSFM. It is concluded that the ample but unbalanced food resources for salmon in the BPr, primarily sprat, induce M74. By reducing the \ufb01shing pressure on cod (Gadus morhua) and by more effectively managing the sprat \ufb01shery in years when the cod stock is weak, the incidence of the M74 syndrome could be reduced and even prevented

The thiamine deficiency syndrome M74, a reproductive disorder of Atlantic salmon (Salmo salar) feeding in the Baltic Sea, is related to the fat and thiamine content of prey fish

This study clari\ufb01es how the diet of Baltic salmon leads to thiamine de\ufb01ciency in eggs, and consequently to M74 mortality of yolk-sac fry. The main prey species, sprat (Sprattus sprattus) and herring (Clupea harengus membras), and their biomass in the Baltic Proper (BPr) and the Bothnian Sea, the two feeding grounds of salmon originating from the northern Gulf of Bothnia rivers, are compared. The thiamine concentration of both prey species is lowest in the youngest age groups. Because average fat content and energy density are greater in sprat than in herring, and greatest in youngest sprat, the supply of thiamine per unit energy is least in a diet containing many young sprat. Also, the greater is the supply of thiamine and fat from sprat in the southern BPr in the preceding year, the lower the concentration of thiamine in salmon eggs. Thiamine de\ufb01ciency in eggs results from an unbalanced diet abundant in fatty prey \ufb01sh, such as young sprat, from which the supply of thiamine is insuf\ufb01cient in proportion to the supply of energy and unsaturated fatty acids for salmon, which must undergo a long prespawning fasting period

Effects of palbociclib in oral squamous cell carcinoma and the role of PIK3CA in conferring resistance

Objective: Lack of effective therapies remains a problem in the treatment of oral squamous cell carcinoma (OSCC), especially in patients with advanced tumors. OSCC development is driven by multiple aberrancies within the cell cycle pathway, including amplification of cyclin D1 and loss of p16. Hence, cell cycle inhibitors of the CDK4/6-cyclin D axis are appealing targets for OSCC treatment. Here, we determined the potency of palbociclib and identified genetic features that are associated with the response of palbociclib in OSCC. Methods: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib response. Results: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar concentrations. Consistently, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin El protein levels. We further demonstrated that the combination of a PI3K/mTOR inhibitor (PF-04691502) and palbociclib completely controlled tumor growth in mice. Conclusions: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies