Journal Club #11: Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway

The programmed death 1 (PD-1) receptor and its ligands programmed death ligand 1 (PD-L1) and PD-L2, members of the CD28 and B7 families, play critical roles in T cell coinhibition and exhaustion. Overexpression of PD-L1 and PD-1 on tumor cells and tumor-infiltrating lymphocytes, respectively, correlates with poor disease outcome in some human cancers. Monoclonal antibodies (mAbs) blockading the PD-1/PD-L1 pathway have been developed for cancer immunotherapy via enhancing T cell functions. Clinical trials with mAbs to PD-1 and PDL1 have shown impressive response rates in patients, particularly for melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), and bladder cancer. Further studies are needed to dissect the mechanisms of variable response rate, to identify biomarkers for clinical response, to develop small-molecule inhibitors, and to combine these treatments with other therapies.

Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 2015 Jan;21(1):24-33.

                                                                                                                                                    

Human cancer immunotherapy with anti-programmed death 1 (PD-1) receptor and anti-programmed death ligand 1 (PD-L1)/L2 antibodies (from Ohaegbulam et al).    

          

Journal Club #10: Calretinin immunohistochemistry as a tool to diagnose Hirschsprung disease

Diagnosis of Hirschsprung disease (HD) is quite entirely based on the histopathological analysis of suction rectal biopsies.This hematoxylin and eosin approach has some limitations, despite the help of acetylcholinesterase staining. pathologist.  [...] Calretinin immunohistochemistry overcomes most of the difficulties encountered using the combination of histology and acetylcholinesterase staining, and detects almost all cases of HD with confidence, with no false positives.

Guinard-Samuel V, et al. Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease. Mod Pathol. 2009 Oct;22(10):1379-84.

Bibliography.

Barshack I, et al. The loss of calretinin expression indicates aganglionosis in Hirschsprung's disease. J Clin Pathol. 2004 Jul;57(7):712-6.

Kapur RP. Calretinin-immunoreactive mucosal innervation in very short-segment Hirschsprung disease: a potentially misleading observation. Pediatr Dev Pathol.2014 Jan-Feb;17(1):28-35.

Szylberg L, Marszałek A. Diagnosis of Hirschsprung's disease with particular emphasis on histopathology. A systematic review of current literature. Prz Gastroenterol. 2014;9(5):264-9.

Journal Club #9: Focal myositis, an intramuscular mass-like reactive process.

Focal myositis is an uncommon inflammatory pseudotumor of skeletal muscle that can be confused with a variety of neoplastic and inflammatory diseases. It is often misunderstood because it presents as a tumor-like mass, but histologically resembles a skeletal muscle myopathy or dystrophy. [...] Histologically, these were solitary intramuscular processes composed of variable myopathic and focal neurogenic changes, fibrosis, and inflammation, occasionally accompanied by prominent eosinophils.[...] Clinical diagnostic considerations ranged from benign entities such as rhabdomyoma, intramuscular lipoma, fibromatosis, myositis ossificans, proliferative myositis, inflammatory myofibroblastic tumor, and inflammatory myopathy to malignant entities such as rhabdomyosarcoma, leiomyosarcoma, liposarcoma, and lymphoma. Available follow-up revealed spontaneous regression.[...] Careful attention to reproducible clinicopathologic features can aid diagnosis and spare patients from excessive surgery or adverse therapy.

Auerbach A, et al. Focal myositis: a clinicopathologic study of 115 cases of an intramuscular mass-like reactive process. Am J Surg Pathol. 2009 Jul;33(7):1016-24.

Bibliography.

Layfield LJ, Crim J, Gupta D. Fine-needle aspiration findings in nodular myositis: a case report. Diagn Cytopathol. 2000 Nov;23(5):343-7

Journal Club #3: H. pylori detected by PCR-based technique.

PCR-based techniques may substitute the hystochemical and immunohistochemical stainings in the detection of H. pylori in gastric biopsy. Moreover, these new assays can identify mutations that predict antibiotic resistance, avoiding the time-consuming coltures.

Bibliography.

Schmitt BH, Regner M, Mangold KA, Thomson RB Jr, Kaul KL. PCR detection of clarithromycin-susceptible and -resistant Helicobacter pylori from formalin-fixed, paraffin-embedded gastric biopsies. Mod Pathol. 2013 Sep;26(9):1222-7.

Weiss J, Tsang TK, Meng X, Zhang H, Kilner E, Wang E, Watkin W. Detection of Helicobacter pylori gastritis by PCR: correlation with inflammation scores and immunohistochemical and CLOtest findings. Am J Clin Pathol. 2008 Jan;129(1):89-96.

Yantiss RK, Lamps LW. To stain or not to stain...That remains the question. Am J Clin Pathol. 2012 Mar;137(3):343-5. 

Comment on

Hartman DJ, Owens SR. Are routine ancillary stains required to diagnose Helicobacter infection in gastric biopsy specimens? An institutional quality assurance review. Am J Clin Pathol. 2012 Feb;137(2):255-60.

Journal Club #2 - Tumor budding as prognostic marker in colorectal cancer

Tumor budding (defined as single neoplastic cells or clusters up to five cells at the invasive front of CRC) may represent a new prognostic marker in colorectal cancer. In particular, it could be useful to indentify those pT3N0M0 "high risk" patients who may benefit of additional therapeutic regimen.

Interestingly, tumor budding can be assessed also in pre-operative biopsy and in cancers other than CRCs. 

Overview of the histomorphological and molecular features of the tumour centre, invasive front and tumour buds in CRC. Reproduced from Zlobec and Lugli, 2010.

Bibliography.

Wang LM, Kevans D, Mulcahy H, O'Sullivan J, Fennelly D, Hyland J, O'Donoghue D, Sheahan K. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer. Am J Surg Pathol. 2009 Jan;33(1):134-41.

Lugli A, Karamitopoulou E, Zlobec I. Tumour budding: a promising parameter in colorectal cancer. Br J Cancer. 2012 May 22;106(11):1713-7. doi: 10.1038/bjc.2012.127. Epub 2012 Apr 24. Review. 

Rogers AC, Gibbons D, Hanly AM, Hyland JM, O'Connell PR, Winter DC, Sheahan K. Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy. Mod Pathol. 2014 Jan;27(1):156-62.

Giger OT, Comtesse SC, Lugli A, Zlobec I, Kurrer MO. Intra-tumoral budding in preoperative biopsy specimens predicts lymph node and distant metastasis in patients with colorectal cancer. Mod Pathol. 2012 Jul;25(7):1048-53.

Sarioglu S, Acara C, Akman FC, Dag N, Ecevit C, Ikiz AO, Cetinayak OH, Ada E; for Dokuz Eylül Head and Neck Tumour Group (DEHNTG). Tumor budding as a prognostic marker in laryngeal carcinoma. Pathol Res Pract. 2010 Feb 15;206(2):88-92.

Liang F, Cao W, Wang Y, Li L, Zhang G, Wang Z. The prognostic value of tumor budding in invasive breast cancer. Pathol Res Pract. 2013 May;209(5):269-75.