Ancillary immunohistochemistry testing for loss of p16 in melanoma: A systematic review and meta-analysis of diagnostic accuracy studies.

BACKGROUND: Ancillary immunohistochemistry testing for p16 loss has been proposed as a diagnostic tool for melanoma, but its accuracy remains uncertain. METHODS: A systematic review and meta-analysis were conducted on 26 studies involving 979 melanomas and 974 nevi. RESULTS: Through bivariate analysis of data across all cut-off values, the sensitivity and specificity were calculated to be 0.55 (95% confidence interval [CI]: 0.38, 0.70) and 0.85 (95% CI: 0.70, 0.94), respectively. Summary estimates of diagnostic accuracy fell below recommended thresholds for effective tests, but subgroup analysis suggested that p16 loss could aid in diagnosing ambiguous lesions as melanoma in certain scenarios. However, the presence of p16 expression in these contexts does not definitively rule out melanoma. The findings were limited by underpowered exploratory study designs at risk for bias in patient selection and test interpretation. CONCLUSIONS: While the use of p16 immunohistochemistry for detecting melanoma is not universally reliable, it may serve as a confirmatory test in differential diagnoses involving common, congenital, acral, Spitz, and deep penetrating nevi. Nevertheless, further studies are needed to validate its utility. Until then, the application of p16 immunohistochemistry in melanoma diagnosis should be regarded as experimental.

Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy.

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11-/- mice. Moreover, in Hoxa11+/- mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.