The lower brain stem of 25 pathologically-confirmed Parkinson's disease (PD) cases was examined by alpha synuclein immunohistochemistry to characterize pathological accumulation of alpha synuclein (Lewy-type α-synucleinopathy, LTS) in the medulla oblongata, to examine differences between affected regions and test a proposed model of staging of pathology in PD. All cases had LTS in the medulla, including the dorsal motor nucleus of the vagus (dmX), when present. The distribution followed a consistent pattern and appeared to be concentrated in a tyrosine hydroxylase (TH) immunoreactive region, probably representing the dorsal IX/X nuclear complex and the intermediate reticular zone. LTS density was greatest in the dmX. A similar distribution pattern to PD was seen in 14 incidental Lewy body disease (ILBD) cases, five derived from the Queen Square Brain Bank tissue collection and nine identified in separate series of 60 neurologically-normal individuals, and in three cases with the G2019S mutation of LRRK2. Semiquantitative assessment showed that severity of pathology in the dmX was not correlated with the severity of cortical pathology. Semiquantitative assay of TH and ChAT peptide expression in the medulla showed that TH expression in PD and ILBD did not differ from controls. These findings broadly support the Braak hypothesis of caudo-rostral development but indicate that the extent of the disease in the cortex and the severity of pathology in the medulla were independent of one another.

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Angiogenesis plays a differential role in various B cell lymphomas. Aggressive lymphomas express the potential molecular therapeutic targets VEGF and COX2, and have higher MVD. In a few low proliferation-fraction lymphomas, Flk-1 might have a role in proliferative advantage. Therapeutic strategies aimed at angiogenesis should take into account lymphoma heterogeneity.

Neuroendocrine differentiation in non-small cell lung cancer is a common feature, which has caused contradictory conclusions concerning survival estimates and responsiveness to therapy. Aiming to clarify this conflict, we analyzed neuroendocrine differentiation by immunohistochemistry in 405 surgically resected non-small cell lung carcinomas using standardized tissue microarray platform and the currently recommended antibody panel consisting of chromogranin-A, synaptophysin, and neural-cell adhesion molecule. Diagnostic criteria provided by the World Health Organization were applied. Histological subtypes were primarily reclassified according to current guidelines, assisted by auxiliary immunohistochemistry. Extensive clinical data was acquired, enabling detailed clinicopathological correlation. Importantly, neuroendocrine differentiation assessed by immunohistochemistry showed no significant relation to overall survival estimates, which remained unaffected by histological subtype, neuroendocrine marker type, adjuvant therapy, and recurring disease. The only exception was a small group consisting of three large cell carcinomas, each expressing all three neuroendocrine markers and demonstrating decreased survival. In conclusion, additional immunohistochemical detection of neuroendocrine differentiation in non-small cell lung cancer is presently not of prognostic importance and does not justify a distinct consideration.

Our comprehensive data would be compatible with a two-step process leading to loss of p16 expression in NSCLC. Hypermethylation of the promoter region may represent an early event, followed by heterozygous deletion of the p16 locus. Because of the possibility of detection of hypermethylated gene regions, these data may lead to the identification of specific patient subgroups more likely to benefit from upcoming demethylating treatment strategies.

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The histologic subtype of non-small cell lung cancer (NSCLC) determines treatment strategies and the need for genetic analyses. Since most NSCLC are diagnosed on small biopsy or cytologic specimens, an accurate but tissue-sparing approach is necessary. To date, consensus for a general diagnostic algorithm is lacking. To test the diagnostic and clinical relevance of the recently published multidisciplinary guidelines by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, we examined 371 surgically resected NSCLCs brought into tissue microarray format. The antibody panel thyroid transcription factor-1 (TTF-1), p63, cytokeratin (CK)5/6, and CK7 is diagnostic for most cases (>94%). Faint/focal staining for CK7 is negligible for classificatory purposes. Grading adenocarcinomas according to histologic architecture is prognostically significant (median overall survival for well/moderate differentiation, 72.5 months; for poor differentiation, 38.5 months; P = .019). Double stains combining the aforementioned nuclear and membranous markers are highly diagnostic for NSCLC, conserving tumor tissue for subsequent analyses.