Hiroyuki Takahata

Analysis of genomic homology of murine gammaherpesvirus (MHV)-72 to MHV-68 and impact of MHV-72 on the survival and tumorigenesis in the MHV-72-infected CB17 scid/scid and CB17+/+ mice

Murine gammaherpesvirus (MHV)‐68‐infected mice are well‐known as models for Epstein–Barr virus (EBV)‐related lymphoproliferative diseases. MHV‐72 may be a relative of MHV‐68, but any genetic comparison between the two (except for the M7 gene) has never been reported. The genetic compositions of MHV‐72 and MHV‐68 were compared and the pathology of MHV‐72 infection studied in CB‐17 severe combined immunodeficiency (scid/scid; SCID) and CB17 wild‐type (CB17+/+) mice. The MHV‐72 DNA sequence was almost identical to MHV‐68 except for approximately 7000 bp corresponding to the MHV‐68 M1–M3 genes. Twenty‐seven of 30 MHV‐72‐infected SCID mice (90%) died from generalized infection with intranuclear viral inclusions for approximately 1 month, while MHV‐72‐infected CB17+/+ mice recovered from acute infection. Long observation and pathological study of 68 MHV‐72‐infected mice for up to 24 months revealed that the survival rate (29.4%) and survival time (21.3 months) of MHV‐72‐infected CB17+/+ mice were significantly lower (P = 0.0127) and shorter (P = 0.0065) than those of the controls (61.1% and 22.9 months), respectively. The malignancy development rate (60.3%) of the infected CB17+/+ mice was also significantly higher (P = 0.004) than those of the controls (22.2%). However, no MHV‐72 DNA was detected in the tumors of infected mice. MHV‐72 may have some tumor‐promoting effects but the tumorigenesis in infected CB17+/+ mice is different from EBV‐associated tumors.

CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine.

Follicular lymphoma (FL) shows co‐expression of B‐cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa‐associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10down) GI‐FL. The diagnosis of CD10down FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10down GI‐FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P < 0.001). The difference was additionally significant between GI‐FL and nodal FL when the analysis was confined to primary GI‐FL (55.2% vs 3.5%, P < 0.001). Compared to CD10+ GI‐FL, CD10down GI‐FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10down group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa‐associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10down GI‐FL, and an identical clone was found between CD10down follicles and CD10+BCL2+ neoplastic follicles. In the diagnosis of cases with CD10down BCL2+ follicles, careful examination with molecular studies should be carried out.

Re-classification of pTNM staging for lung cancer: single-institution report at a Japanese comprehensive cancer hospital.

Among the major cancer sites, the lung has the most complicated pTNM description. Reclassification of International Union Against Cancer (UICC)‐pTNM grading of 262 lung cancers resected at Shikoku Cancer Center was done using microscopy and audit of pathology reports. Of the 262 lung cancers, 222 were obtained at operation from 1999 to 2004 and 40 additional cases from 2006. Among 666 pTNM components of the former cases, 37 components (31T, 3N, 3M) in 35 cases were revised to different categories. The concordance rate (CR) of the original stage to the reclassified stage was 90% (210/222) in the five‐group staging system (5GSS) without subdivisions and 84% (187/222) in the 8GSS with subdivisions such as IA and IB. It decreased in advanced cases. For example, the CR was higher in stage I (97%, 158/163) than in stage II–IV (88%, 51/59) in five‐GSS (χ2 test, P < 0.05). The CR in 8GSS of the additional 40 cases, which were diagnosed after the review of the former 222 cases, was 98% (39/40), indicating that the knowledge gained from the review improved the accuracy significantly (χ2 test, P < 0.05). It is necessary to assess disparities in the accuracy of pTNM for lung cancer at each institution. This is also true for cancers at other sites.